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Commit 70347a62 authored by Asal Sahami Moghaddam's avatar Asal Sahami Moghaddam
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Merge branch 'main' of ssh://gitlab.igem.org/2024/bielefeld-cebitec

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code/cit.py
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# Voraussetzungen
#- Python 3.x
#- bibtexparser (Installieren Sie es mit `pip install bibtexparser`)
# use like: python3 cit.py -i bibtex.bib -s 1
problemlist = []
......
src/components/BFH-Timeline.tsx
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− 13
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......@@ -10,25 +10,45 @@ export function BFHTimeline () {
Begin & Opening
</div>
<TimelineItemTwoPic
<TimelineItemPic
url="https://static.igem.wiki/teams/5247/photos/meetup/speakers/ram.jpg"
date='Scientific Talk I.'
tag= 'Talks'
color='var(--lightblue)'
csstag="talkone"
vorname="Ram"
nachname="Shakar"
heading="AI-Driven Breakthroughs in Plasmid DNA Production"
text="Ram Shankar from Plasmid Factory delves into the integration of AI in advancing plasmid DNA technology for gene therapy. Highlighting real-world applications, he demonstrates how AI optimizes plasmid purification, enhances gene vector stability, and accelerates mRNA production, offering a glimpse into the future of biotech innovations."
>
<div id="talkone" style={{display: "none"}}>
<p>Ram Shankar, from Plasmid Factory, gave an insightful talk about the integration of AI and advanced biotechnology, with a focus on plasmid DNA production. His presentation highlighted how AI-driven innovations have transformed research methodologies in gene therapy, plasmid manufacturing, and DNA purification. His speech showcased the practical applications of AI in streamlining workflows, making biotech processes more efficient and scalable.</p>
<p>Shankar began by illustrating how scientific advancements, such as powered flight and DNA research, have rapidly progressed within a single human lifetime. He connected this concept to breakthroughs in plasmid DNA technology, where Plasmid Factory’s work has been pivotal in advancing gene therapy products. A key takeaway was the integration of AI in optimizing plasmid purification processes, enabling the production of high-quality plasmids and mini circles for clinical applications.
Shankar also introduced real-world examples, such as the use of AI in enhancing the stability and quality of gene vectors and mRNA production. His discussion of collaborations between academia and industry underscored the importance of networking and shared innovation, comparing it to the historic partnership between Stanley Cohen and Herbert Boyer that revolutionized recombinant DNA technology.
</p>
<p>
The talk provided attendees with a deeper understanding of how AI can revolutionize lab work, particularly in scaling up DNA production for gene therapies. By applying these insights, participants left with ideas on how to leverage AI to enhance their own research projects, particularly in biotechnology and gene editing.
</p>
</div>
</TimelineItemPic>
<TimelineItemPic
url="https://static.igem.wiki/teams/5247/photos/hp/kristian.jpeg"
url2="https://static.igem.wiki/teams/5247/photos/meetup/speakers/ram.jpg"
date='Scientific Talk I.'
tag= 'Talks'
color='var(--lightblue)'
csstag="talkone"
csstag="talkonek"
vorname="Kristian"
vorname2="Ram"
nachname="Müller"
nachname2="Shakar"
heading="placeholder"
text="Lorem ipsum dolor sit amet, consetetur sadipscing elitr, sed diam nonumy eirmod tempor invidunt ut labore et dolore magna aliquyam erat, sed diam voluptua. At vero eos et accusam et"
>
<div id="talkone" style={{display: "none"}}>
So much more
heading=""
text=""
>
<div id="talkonek" style={{display: "none"}}>
Ask Sinan
</div>
</TimelineItemPic>
</TimelineItemTwoPic>
<TimelineItemPic
url="https://static.igem.wiki/teams/5247/photos/meetup/speakers/christian-kolland.png"
date='How to Wiki'
......@@ -41,7 +61,24 @@ export function BFHTimeline () {
text="Learning the basics of Wiki coding and design. In this workshop, the participants geined expertise to elevate their teams wiki."
>
<div id="wikiworkshop" style={{display: "none"}}>
so much more
<br/>
<p>We participated in an intensive workshop on HTML and CSS made by a former iGEM participant of team GU-Frankfurt 2023 and head of wiki,
Christian Kolland. All participants gain an overview of the essentials for building websites. </p>
<p>The session began with an introduction to color theory tools such as Realtime Colors and AI Colors, emphasizing their role in creating visually
appealing designs. Typography was a key focus, clarifying the difference between typeface (e.g., Futura) and font variations (e.g., Futura Condensed),
and how font weights and sizes impact readability and design hierarchy. Practical guidelines, including the usage of different types of units such as
PX or REM for font sizing and understanding spacing for an effective layout, were given. </p>
<p>
We delved into HTML's structure for web content, learning semantic tags for effectively organizing information. CSS principles were explored next,
demonstrating how styles cascade from parent to child elements, which are crucial for consistent design across a webpage.
A significant part of the workshop involved hands-on coding in Visual Studio Code, where we replicated a pre-designed webpage using the HTML and CSS
techniques learned. This exercise equipped the attending iGEM teams with practical skills to create and style their own project websites and emphasized
the importance of component-based design and effective content organization.
</p>
<p>
By the end of the workshop, the attendees were inspired to pursue creating their own wikis, leveraging AI-based tools like for initial designs and imagery.
Overall, we left with a solid foundation in web development and were prepared to build professional and functional websites for their iGEM projects.
</p>
</div>
</TimelineItemPic>
<TimelineItemPic
......@@ -52,8 +89,7 @@ export function BFHTimeline () {
csstag="synworkshop"
vorname="Traci"
nachname="Haddock"
text="Design genetic constructs and re-write the genomic code, and plan experiments using AI. Learn how to effectively build genetic circuit systems for implementation in your iGEM project.
"
text="Design genetic constructs and re-write the genomic code, and plan experiments using AI. Learn how to effectively build genetic circuit systems for implementation in your iGEM project."
heading="placeholder"
>
......
src/components/PrimeGuide.tsx 0 → 100644
+ 336
− 0
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import { useEffect, useRef, useState } from "react";
export function PrimeGuideAnimOne(){
const [isVisible, setVisible] = useState(false);
const domRef = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible(entry.isIntersecting));
});
observer.observe(domRef.current!);
}, []);
const [isVisible2, setVisible2] = useState(false);
const domRef2 = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible2(entry.isIntersecting));
});
observer.observe(domRef2.current!);
}, []);
const [isVisible3, setVisible3] = useState(false);
const domRef3 = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible3(entry.isIntersecting));
});
observer.observe(domRef3.current!);
}, []);
const [isVisible4, setVisible4] = useState(false);
const domRef4 = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible4(entry.isIntersecting));
});
observer.observe(domRef4.current!);
}, []);
const [isVisible5, setVisible5] = useState(false);
const domRef5 = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible5(entry.isIntersecting));
});
observer.observe(domRef5.current!);
}, []);
return (
<>
{/* One */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible ? '1' : '0'}`,
'visibility': `${isVisible ? 'visible' : 'hidden'}`}}
ref={domRef}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguideone1.webp">
</img>
</div>
{/* Two */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible2 ? '1' : '0'}`,
'visibility': `${isVisible2 ? 'visible' : 'hidden'}`}}
ref={domRef2}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguideone2.webp">
</img>
</div>
{/* Three */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible3 ? '1' : '0'}`,
'visibility': `${isVisible3 ? 'visible' : 'hidden'}`}}
ref={domRef3}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguideone3.webp">
</img>
</div>
{/* Four */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible4 ? '1' : '0'}`,
'visibility': `${isVisible4 ? 'visible' : 'hidden'}`}}
ref={domRef4}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguideone4.webp">
</img>
</div>
{/* Five */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible5 ? '1' : '0'}`,
'visibility': `${isVisible5 ? 'visible' : 'hidden'}`}}
ref={domRef5}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguideone5.webp">
</img>
</div>
</>
);
}
export function PrimeGuideAnimTwo(){
const [isVisible, setVisible] = useState(false);
const domRef = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible(entry.isIntersecting));
});
observer.observe(domRef.current!);
}, []);
const [isVisible2, setVisible2] = useState(false);
const domRef2 = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible2(entry.isIntersecting));
});
observer.observe(domRef2.current!);
}, []);
const [isVisible3, setVisible3] = useState(false);
const domRef3 = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible3(entry.isIntersecting));
});
observer.observe(domRef3.current!);
}, []);
const [isVisible4, setVisible4] = useState(false);
const domRef4 = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible4(entry.isIntersecting));
});
observer.observe(domRef4.current!);
}, []);
const [isVisible5, setVisible5] = useState(false);
const domRef5 = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible5(entry.isIntersecting));
});
observer.observe(domRef5.current!);
}, []);
const [isVisible6, setVisible6] = useState(false);
const domRef6 = useRef(null)!;
useEffect(() => {
const observer = new IntersectionObserver(entries => {
entries.forEach(entry => setVisible6(entry.isIntersecting));
});
observer.observe(domRef6.current!);
}, []);
return (
<>
{/* One */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible ? '1' : '0'}`,
'visibility': `${isVisible ? 'visible' : 'hidden'}`}}
ref={domRef}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguidetwo1.webp">
</img>
</div>
{/* Two */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible2 ? '1' : '0'}`,
'visibility': `${isVisible2 ? 'visible' : 'hidden'}`}}
ref={domRef2}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguidetwo2.webp">
</img>
</div>
{/* Three */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible3 ? '1' : '0'}`,
'visibility': `${isVisible3 ? 'visible' : 'hidden'}`}}
ref={domRef3}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguidetwo3.webp">
</img>
</div>
{/* Four */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible4 ? '1' : '0'}`,
'visibility': `${isVisible4 ? 'visible' : 'hidden'}`}}
ref={domRef4}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguidetwo4.webp">
</img>
</div>
{/* Five */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible5 ? '1' : '0'}`,
'visibility': `${isVisible5 ? 'visible' : 'hidden'}`}}
ref={domRef5}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguidetwo5.webp">
</img>
</div>
{/* Six */}
<div
className='col'
style={{
'height': '100vh',
'transition': 'opacity 0.6s ease-out',
'opacity': `${isVisible6 ? '1' : '0'}`,
'visibility': `${isVisible6 ? 'visible' : 'hidden'}`}}
ref={domRef6}>
<img
style={{
'position': 'fixed',
'top': '20vh',
'left': '20vw',
'width': '60vw',
'height': '60vh',
}}
src="https://static.igem.wiki/teams/5247/landing/primeguide/primeguidetwo6.webp">
</img>
</div>
</>
);
}
\ No newline at end of file
src/contents/Home.tsx
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− 2
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......@@ -2,6 +2,7 @@ import { FadeIn } from "../components/FadeIn";
import { Breathe } from "../components/Breathe";
import { Problems } from "../components/Problems";
import { AirbuddyAnim } from "../components/AirbuddyAnim";
import { PrimeGuideAnimOne, PrimeGuideAnimTwo } from "../components/PrimeGuide";
import { useTabNavigation } from "../utils/TabNavigation";
export function Home() {
......@@ -34,11 +35,15 @@ export function Home() {
<FadeIn filepath="https://static.igem.wiki/teams/5247/landing/gifs/treatment-2.gif" bg=''></FadeIn>
<FadeIn filepath="https://static.igem.wiki/teams/5247/landing/airbuddy.gif" bg=''></FadeIn>
<AirbuddyAnim></AirbuddyAnim>
<FadeIn filepath="https://static.igem.wiki/teams/5247/landing/precyse.gif" bg=''></FadeIn>
<FadeIn filepath="https://static.igem.wiki/teams/5247/landing/airbuddy.gif" bg=''></FadeIn>
<FadeIn filepath="https://static.igem.wiki/teams/5247/landing/primeguide.webp" bg=''></FadeIn>
<PrimeGuideAnimOne></PrimeGuideAnimOne>
<PrimeGuideAnimTwo></PrimeGuideAnimTwo>
<FadeIn filepath="https://static.igem.wiki/teams/5247/landing/precyse.gif" bg=''></FadeIn>
<FadeIn filepath="https://static.igem.wiki/teams/5247/landing/gifs/proofofconcept.gif" bg=''></FadeIn>
{/* Spacing Block */}
<div className='col' style={{ 'height': '100vh' }}></div>
......
src/contents/Human Practices/Further Engagement/Education.tsx
+ 14
− 10
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import { ButtonOne } from "../../../components/Buttons";
import { H4 } from "../../../components/Headings";
import { H5 } from "../../../components/Headings";
import { LoremMedium } from "../../../components/Loremipsum";
......@@ -16,7 +17,6 @@ export function HPEducation(){
<div className="col">
<ButtonOne openclass="edu-cycletab" text="Schüler*innen Akademie" open="akademie"></ButtonOne>
</div>
</div>
<div id="edu-overview" className="edu-cycletab" style={{display: "block"}}>
<H4 id="edu-heading" text="Our education and outreach"/>
......@@ -26,21 +26,25 @@ export function HPEducation(){
</div>
<div id="akademie" className="edu-cycletab" style={{display: "none"}}>
<H4 id="student-academy-heading" text="Student academy on the topic of synthetic biology"/>
<p>The Center for Biotechnology (CeBiTec) at Bielefeld University organizes the annual CeBiTec Student Academy for “Biotechnology and Biomedicine.” Supported by the Osthushenrich Foundation and the Detmold district government, the academy offers students a unique opportunity to deepen their understanding of biology, genetics, and molecular biology through hands-on experiments and expert lectures. Key topics include nanopore sequencing, tumor diagnostics, and the evolution of SARS-CoV-2. The program is especially valuable for students transitioning from school to potential studies in the natural sciences.
<H5 id="Scüler*innen Akademie" text="Teaching the Next Generation of SynBio Pioneers The Center for Biotechnology (CeBiTec) at Bielefeld University organizes the annual CeBiTec Student Academy for “Biotechnology and Biomedicine.” Supported by the Osthushenrich Foundation and the Detmold district government, the academy offers students a unique opportunity to deepen their understanding of biology, genetics, and molecular biology through hands-on experiments and expert lectures. Key topics include nanopore sequencing, tumor diagnostics, and the evolution of SARS-CoV-2. The program is especially valuable for students transitioning from school to potential studies in the natural sciences."/>
<p>
Due to our collaboration with the Student Academy, we conducted the nanopore sequencing experiment and served as teachers, assisting in experiment preparation, execution, offering guidance, and answering questions. This role allowed us to teach the students about laboratory work, the critical aspects of conducting experiments, and essential safety considerations. The experiment involved isolating bacterial DNA, preparing samples for sequencing, and performing both sequencing and data analysis.
Since we presented our iGEM project PreCyse to them as well, the students were introduced to study-related projects like iGEM. They learned about the daily tasks, challenges, and responsibilities involved in iGEM through project discussions. Many students were captivated by the iGEM concept and expressed interest in participating during their future studies. They were particularly fascinated by the opportunity to develop real research projects, work independently in the lab, learn extensively about synthetic biology, and implement creative ideas while collaborating with an international team.</p>
</div>
<div id="teutoruft" className="edu-cycletab" style={{display: "none"}}>
<H4 id="teuroruft-heading" text="Educational city tour for young and old"/>
<p>What is “Der Teuto ruft!” and why did we participate?
<H4 id="teuroruft-heading" text="Educational city tour for young and old"/>
<H5 id="Der Teuto ruft!" text="“Der Teuto ruft!” and why we participate"/>
<p> </p>
</div>
"Der Teuto ruft!" is an outreach event located all over the city of Bielefeld where various local companies and institutions engage with the public to inform them about their work. Since we wanted to raise awareness for cystic fibrosis and present our approach to developing an optimized gene therapy to combat this disease, our participation in the "Der Teuto ruft!" event in Bielefeld was the perfect opportunity to do so.
What was our strategy?
Our goal was to educate children about the challenges faced by CF patients, especially the ones with lung problems. The knowledge which we gained at the Science Communication Workshop as part of the BFH Meetup was the optimal basis to plan our outreach to the public. We engaged the children with activities like coloring lung images and conducting experiments to experience and understand lung related symptoms.
<H5 id="What was our strategy?" text="What is our strategy?"/>
<p>Our goal was to educate children about the challenges faced by CF patients, especially the ones with lung problems. The knowledge which we gained at the Science Communication Workshop as part of the BFH Meetup was the optimal basis to plan our outreach to the public. We engaged the children with activities like coloring lung images and conducting experiments to experience and understand lung related symptoms.
One such experiment involved creating a lung model from balloons and straws, demonstrating the difficulty patients have in breathing by having the children blow into the straws. Additionally, we set up a tank with a mixture of starch and water to simulate mucus and placed a ball on top. The children tried to blow the ball across the surface, illustrating how hard it is for air to move through mucus compared to water, where the ball moved much more easily.
The very little ones could paint coloring pages which we designed and printed for them. For the adults, we provided information about our project and discussed the implications and potential of gene therapy for cystic fibrosis. These conversations made it abundantly clear that degrees of knowledge on this topic widely vary throughout the public and we were happy to fill in the existing gaps in people's knowledge and exchange points of view on gene therapy.
Moreover, we connected with other institutions and participants at the event. We shared our booth at Bielefeld’s “Skulpturenpark” on the outside with btS, the life science student initiative from Bielefeld University [LINK], with whose members we had stimulating discussions as well. We were more than delighted when the city of Bielefeld featured us on their Instagram, highlighting our presence during "Der Teuto ruft!". This collaboration helped us reach a wider audience and raise awareness about our research efforts. What is our conclusion?
Despite the changeable weather, we could educate many people of Bielefeld's community about cystic fibrosis, our therapeutic approach and gene therapy in general and had the opportunity to improve our science communication for the future as well so it was a successful event! </p>
Moreover, we connected with other institutions and participants at the event. We shared our booth at Bielefeld’s “Skulpturenpark” on the outside with btS, the life science student initiative from Bielefeld University [LINK], with whose members we had stimulating discussions as well. We were more than delighted when the city of Bielefeld featured us on their Instagram, highlighting our presence during "Der Teuto ruft!". This collaboration helped us reach a wider audience and raise awareness about our research efforts.</p>
<H5 id="conclusion? " text="What is our conclusion"/>
<p>Despite the changeable weather, we could educate many people of Bielefeld's community about cystic fibrosis, our therapeutic approach and gene therapy in general and had the opportunity to improve our science communication for the future as well so it was a successful event! </p>
<div className="row align-items-center">
<div className="col">
<img src="https://static.igem.wiki/teams/5247/photos/edcation-and-outreach/teutoruft-experminet.jpeg"></img>
......@@ -51,5 +55,5 @@ Despite the changeable weather, we could educate many people of Bielefeld's comm
</div>
</div>
</div>
)
);
}
\ No newline at end of file
src/contents/Human Practices/Further Engagement/Outreach.tsx
+ 15
− 2
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......@@ -18,6 +18,7 @@ export function HPOutreach(){
<ButtonOne openclass="out-cycletab" text="waffel sale" open="waffel sale"></ButtonOne>
</div>
</div>
<div id="out-overview" className="out-cycletab" style={{display: "block"}}>
<H4 id="out-heading" text="Our education and outreach"/>
......@@ -26,7 +27,18 @@ export function HPOutreach(){
<LoremMedium/>
</div>
<div id="waffle sale" className="out-cycletab" style={{display: "none"}}></div>
<div id="waffle sale" className="out-cycletab" style={{display: "none"}}>
<H4 id="waffle sale" text="Waffle sale"/>
<div className="row">
<div className="full-small col3">
</div>
</div>
<div className="col">
<h3>Waffle sale</h3>
<p>To support our research project and raise funds for our iGEM team at Bielefeld University, we decided to organize a waffle sale in the main hall of the university. This initiative was aimed at raising awareness about our project and collecting funds for our research into cystic fibrosis. </p>
<p>The sale took place in cystic fibrosis awareness month May in the Great Hall of our University. As people passed by, we engaged them by introducing our research group and explaining our project’s objectives. We shared information about cystic fibrosis and why we are raising money. Our goal was to not only just to sell waffles, but also to educate the university community about our research and its’ potential impact. The response has been overwhelmingly positive. Many were genuinely interested in our work and asked for more details about our research and the goals of our project. This enthusiasm strengthened our commitment to the project and highlighted the importance of community involvement in scientific research. </p>
<p>The waffle sale was a great success, both in terms of raising funds and increasing awareness about our work within the university. It was a collaborative effort that brought our team closer together and demonstrated the power of community support in advancing scientific research. </p>
</div>
<div id="mukomove" className="out-cycletab" style={{display: "none"}}>
<H4 id="cf-month" text="Cystic fibrosis awareness month"/>
<div className="row">
......@@ -78,5 +90,6 @@ export function HPOutreach(){
<p>The MUKOmove was therefore a complete success, and we take pride in having contributed to the goal while raising more awareness for cystic fibrosis in our region and Germany as a whole.</p>
</div>
</div>
)
</div>
);
}
\ No newline at end of file
src/contents/Human Practices/HP-abstract.tsx 0 → 100644
+ 11
− 0
View file @ 70347a62
import { LoremMedium } from "../../components/Loremipsum"
import { Section } from "../../components/sections"
export function HPAbstract(){
return(
<Section title="Abstract" id="Abstract">
<LoremMedium/>
</Section>
)
}
\ No newline at end of file
src/contents/Human Practices/human-practices.tsx
+ 2
− 0
View file @ 70347a62
......@@ -55,6 +55,7 @@ import { HPIntegrated } from "./IHP";
import { HPFurtherEngagement } from "./Further Engagement/FurtherEngagement";
import { HPSupplement } from "./Further Engagement/SupMaterial";
import { useTabNavigation } from "../../utils/TabNavigation";
import { HPAbstract } from "./HP-abstract";
export function HumanPractices() {
useTabNavigation();
......@@ -64,6 +65,7 @@ export function HumanPractices() {
return (
<div className="col">
<HPAbstract/>
<HPOverview/>
<HPIntroduction/>
<HPIntegrated/>
......
src/contents/description.tsx
+ 32
− 7
View file @ 70347a62
......@@ -525,6 +525,12 @@ let symptombuttonrowdata = [
function createSymptomSteckbrief(data: SymptomDatensatz){
let examplelist = [];
for (let index = 0; index < data.subsections.length; index++) {
let absaetze = []
for (let i = 0; i < data.subsections[index].text.length; i++) {
absaetze.push(
<p>{data.subsections[index].text[i]}</p>
)
}
examplelist.push(
<div className="drug">
<H4 text={data.subsections[index].title}/>
......@@ -535,13 +541,20 @@ function createSymptomSteckbrief(data: SymptomDatensatz){
return(
<div>
<H4 id={`${data.name}-btn`} text={stringToSlug(data.name)}/>
<div className="col-2">
<div className="symptom-img-wrapper">
<img src={data.picture} className="symptom-img"/>
<div className="row">
<div className="col-2">
<div className="symptom-img-wrapper">
<img src={data.picture} className="symptom-img"/>
</div>
</div>
<div className="col">
{data.introduction}
</div>
</div>
<div className="col">
{examplelist}
</div>
</div>
)
......@@ -551,6 +564,13 @@ function createSymptomSteckbrief(data: SymptomDatensatz){
function createDrugSteckbrief(data: DrugDatensatz){
let examplelist = [];
for (let index = 0; index < data.examples.length; index++) {
let absaetze = []
for (let i = 0; i < data.examples[index].text.length; i++) {
absaetze.push(
<p>{data.examples[index].text[i]}</p>
)
}
examplelist.push(
<div className="drug">
<H4 text={data.examples[index].title}/>
......@@ -562,9 +582,14 @@ function createDrugSteckbrief(data: DrugDatensatz){
return(
<div>
<H4 id={`${data.name}-btn`} text={stringToSlug(data.name)}/>
<div className="col-2">
<div className="symptom-img-wrapper">
<img src={data.picture} className="symptom-img"/>
<div className="row">
<div className="col-2">
<div className="symptom-img-wrapper">
<img src={data.picture} className="symptom-img"/>
</div>
</div>
<div className="col">
{data.introduction}
</div>
</div>
<div className="col">
......
src/contents/safety.tsx
+ 78
− 20
View file @ 70347a62
......@@ -19,43 +19,72 @@ export const Safety: React.FC = () =>{
<div>
<p>
As part of our project to develop a prime-editing complex to correct the F508del mutation in cystic fibrosis, we place great emphasis on safety at all stages of research. Our final construct will be tested in primary cultures of epithelial cells obtained from nasal swabs, isolated from both patients and healthy individuals. from nasal swabs [link primär Kulturen]. To guarantee safety and ensure the highest level of precision and reliability of our results, we have introduced a series of carefully planned checkpoints during the experiments. These milestones allow for continuous monitoring, timely adjustments and validation at each critical stage. This ensures that potential issues are identified and addressed immediately, minimizing risk and improving the overall quality of the experimental results. [link zu den Experimenten] . iGEM places great emphasis on biosafety, ensuring that all projects adhere to strict safety standards. One of these measures is the iGEM White List, which includes organisms and parts that are pre-approved for use based on their safety profile. Any components or organisms not covered by this White List must be submitted as 'Check-ins' to the iGEM Safety Committee for approval. Check-ins are formal safety evaluations that allow the committee to assess the potential risks and ensure proper containment and handling procedures are in place. Although we used some parts and organisms that were not included on the White List, these were assessed as critical for our project and submitted as Check-ins to the iGEM Safety Committee. Furthermore, we were in active exchange with the committee throughout the process. The Check-ins provide a clear picture of the biosafety aspects of our project, reflecting our commitment to safety and compliance with iGEM standards.
The main safety measures we have implemented include:
<br/><strong>Compliance with S1 conditions:</strong> Working in S1 laboratories ensures that only organisms in the lowest risk group are used, minimizing the risk to humans and the environment.
<br/><strong>Sterile working practices:</strong> To avoid contamination, we have implemented strict hygiene measures, including the disinfection of work surfaces and the correct disposal of biological waste.
<br/><strong>Controlled access:</strong> Access to laboratories was strictly regulated to ensure that only trained personnel worked with the genetically modified organisms and cell lines.
<br/><strong>Documentation:</strong> All work steps, materials used and cell lines were carefully documented to ensure traceability and safety.
<br/><strong>Safe handling of cell lines:</strong> The cell lines used for experiments were handled in accordance with the applicable safety regulations. This included regular checks for contamination and the safe storage and disposal of cell cultures.
The main safety measures we have implemented include:
</p>
<p>
<strong>Compliance with S1 conditions:</strong> Working in S1 laboratories ensures that only organisms in the lowest risk group are used, minimizing the risk to humans and the environment.
</p>
<p>
<strong>Sterile working practices:</strong> To avoid contamination, we have implemented strict hygiene measures, including the disinfection of work surfaces and the correct disposal of biological waste.
</p>
<p>
<strong>Controlled access:</strong> Access to laboratories was strictly regulated to ensure that only trained personnel worked with the genetically modified organisms and cell lines.
</p>
<p>
<strong>Documentation:</strong> All work steps, materials used and cell lines were carefully documented to ensure traceability and safety.
</p>
<p>
<strong>Safe handling of cell lines:</strong> The cell lines used for experiments were handled in accordance with the applicable safety regulations. This included regular checks for contamination and the safe storage and disposal of cell cultures.
</p>
<H4 text="Checkin for the Prime-Editing Komplex "></H4>
<p>
<strong>Reverse transcriptase:</strong> Reverse transcriptase plays a central role in prime editing by specifically inserting the correction as DNA at the inserted nick using an RNA template provided by pegRNA. The correction of the complementary DNA strand then takes place via the natural cell repair mechanisms. This ensures an exact correction of the target sequence. We checked the reverse transcriptase to ensure it could perform precise genome editing without introducing unintended mutations. This was important to minimize the risk of off-target effects that could lead to unexpected or harmful consequences.
<br/><strong>pegRNA (Prime Editing Guide RNA):</strong> The pegRNA is a multifunctional RNA molecule that fulfils two essential tasks. Firstly, it serves as a standard <strong>guide RNA (gRNA)</strong> that binds specifically to the target DNA and thus marks the site of editing. Secondly, it contains an RNA template that encodes the desired DNA modification. This enables the precise integration of the genetic modifications at the target site. We evaluated pegRNA for its ability to specifically target and modified the intended DNA sequence. Ensuring its specificity was crucial to avoid the potential disruption of other genes.
<br/><strong>Nickase Cas9, CasX, Fanzor (SpuFz1):</strong> These modified nucleases are designed to cut only one strand of DNA. This leads to controlled and precise editing of the genome, as cutting only one strand minimizes the risk of unwanted double-strand breaks. CasX and Fanzor offer smaller alternatives to Cas9, which is particularly advantageous for use in cells or organisms where space and efficiency requirements in terms of the transport system are an issue. Fanzor, being a newly introduced endonuclease, was particularly scrutinized in our project to ensure its safety and effectiveness in different cellular contexts.
<br/>This prime-editing complex thus represents a precise and efficient method for gene editing. By combining these components, genetic modifications can be performed with minimal side effects
</p>
<p>
<strong>pegRNA (Prime Editing Guide RNA):</strong> The pegRNA is a multifunctional RNA molecule that fulfils two essential tasks. Firstly, it serves as a standard guide RNA (gRNA) that binds specifically to the target DNA and thus marks the site of editing. Secondly, it contains an RNA template that encodes the desired DNA modification. This enables the precise integration of the genetic modifications at the target site. We evaluated pegRNA for its ability to specifically target and modified the intended DNA sequence. Ensuring its specificity was crucial to avoid the potential disruption of other genes.
</p>
<p>
<strong>Nickase Cas9, CasX, Fanzor (SpuFz1):</strong> These modified nucleases are designed to cut only one strand of DNA. This leads to controlled and precise editing of the genome, as cutting only one strand minimizes the risk of unwanted double-strand breaks. CasX and Fanzor offer smaller alternatives to Cas9, which is particularly advantageous for use in cells or organisms where space and efficiency requirements in terms of the transport system are an issue. Fanzor, being a newly introduced endonuclease, was particularly scrutinized in our project to ensure its safety and effectiveness in different cellular contexts.
This prime-editing complex thus represents a precise and efficient method for gene editing. By combining these components, genetic modifications can be performed with minimal side effects
</p>
<H4 text="Checkin for Cloning"></H4>
<p>
For our cloning experiments and the development of our prime editing complexes, we have amplified various plasmids in <i>E. coli</i> K-12 strains (DH5α,10-Beta) When working with microbial strains such as E. coli K-12 strains, a it's important to consider potential risks associated with their use, even though they are generally regarded as safe in laboratory settings. All experiments were performed under strict S1 conditions, following all relevant safety protocols. Below you will find an overview of the E.coli K-12 strains for our cloning experiments, submitted by us as a checkin and the specific safety measures:
<br/><i>E. coli K-12</i> strains (DH5α,10-Beta): Although these strains are non-pathogenic and have been modified to minimize the risk of spreading antibiotic resistance, there remains a low risk of horizontal gene transfer, where genetic material could be transferred to other microorganisms, potentially leading to the spread of resistance genes or other traits. If accidentally released into the environment, E. coli K-12 strains could potentially interact with native microbial communities. While they are typically outcompeted in natural environments, there's a remote possibility of ecological disruption, particularly in microenvironments where they could find a niche.While these strains are non-virulent, they still pose a minimal risk to humans, particularly immunocompromised individuals, through accidental ingestion or inhalation in a laboratory setting.
For our cloning experiments and the development of our prime editing complexes, we have amplified various plasmids in <i>E. coli</i> K-12 strains (DH5α,10-Beta) When working with microbial strains such as <i>E. coli</i> K-12 strains, a it's important to consider potential risks associated with their use, even though they are generally regarded as safe in laboratory settings. All experiments were performed under strict S1 conditions, following all relevant safety protocols. Below you will find an overview of the <i>E. coli</i> K-12 strains for our cloning experiments, submitted by us as a checkin and the specific safety measures:
</p>
<p>
<strong><i>E. coli K-12</i> strains (DH5α,10-Beta):</strong> Although these strains are non-pathogenic and have been modified to minimize the risk of spreading antibiotic resistance, there remains a low risk of horizontal gene transfer, where genetic material could be transferred to other microorganisms, potentially leading to the spread of resistance genes or other traits. If accidentally released into the environment, <i>E. coli</i> K-12 strains could potentially interact with native microbial communities. While they are typically outcompeted in natural environments, there's a remote possibility of ecological disruption, particularly in microenvironments where they could find a niche.While these strains are non-virulent, they still pose a minimal risk to humans, particularly immunocompromised individuals, through accidental ingestion or inhalation in a laboratory setting.
</p>
<p>
We submitted the yeast strain <i>Pichia pastoris</i> (SMD1163) for the protein expression of Fanzor.
<br/><i>Pichia pastoris</i> (SMD1163): <i>Pichia pastoris</i> (SMD1163) is a widely used yeast strain for the expression of recombinant proteins. It is characterized by a methanol-inducible expression system (AOX1 promoter) and high cell growth rates, which makes it ideal for industrial applications. The strain can be easily genetically manipulated and can perform post-translational modifications, which supports correct protein production.
<br/>When working with <i>Pichia pastoris</i> (SMD1163), various safety-relevant aspects must be observed. Although the organism is considered non-pathogenic and biologically safe (S1), skin contact and aerosol formation should be avoided to minimize the risk of infection or allergic reactions. When using genetically modified strains, it is important to follow the relevant GMO guidelines to prevent uncontrolled release. In addition, handling chemicals such as methanol requires special precautions as they are toxic and highly flammable. The disposal of cell cultures and waste must also be carried out in accordance with biosafety regulations, especially in the case of genetically modified organisms.
</p>
<p>
<strong><i>Pichia pastoris</i> (SMD1163):</strong> <i>Pichia pastoris</i> (SMD1163) is a widely used yeast strain for the expression of recombinant proteins. It is characterized by a methanol-inducible expression system (AOX1 promoter) and high cell growth rates, which makes it ideal for industrial applications. The strain can be easily genetically manipulated and can perform post-translational modifications, which supports correct protein production.
When working with <i>Pichia pastoris</i> (SMD1163), various safety-relevant aspects must be observed. Although the organism is considered non-pathogenic and biologically safe (S1), skin contact and aerosol formation should be avoided to minimize the risk of infection or allergic reactions. When using genetically modified strains, it is important to follow the relevant GMO guidelines to prevent uncontrolled release. In addition, handling chemicals such as methanol requires special precautions as they are toxic and highly flammable. The disposal of cell cultures and waste must also be carried out in accordance with biosafety regulations, especially in the case of genetically modified organisms.
</p>
<H4 text="Checkin for Testing in cell lines "></H4>
<p>
In our project, we paid attention to safety at every step, especially when working with specific cell lines [link Zellinien]. All experiments were performed under strict S1 conditions, following all relevant safety protocols. Given the sensitivity of the human cell lines we used, we placed great emphasis on controlled and well-designed workflows. All transfections were performed in our own transfection laboratory to ensure a high level of safety and compliance. Below you will find an overview of the cell lines submitted by us as a checkin and the specific safety measures:
HEK293T-3HA-CFTR.
The HEK293T-3HA-CFTR cell line is based on HEK293T cells expressing an additional tsA1609 allele of the SV40 large T antigen. This allele enables the replication of vectors containing the SV40 origin of replication. In addition to the native CFTR gene, which is not expressed in HEK cells, the HEK293T-3HA-CFTR cell line from Leuven carries another copy of the CFTR gene embedded in an expression cassette. This cassette contains a CMV promoter, which is derived from the human cytomegalovirus and is frequently used for the overexpression of genes in human cells. In addition, the cassette contains a puromycin resistance gene that is co-expressed with CFTR, allowing continuous selection of CFTR-expressing cells.
<br/><br/><strong>HEK293T-3HA-F508del-CFTR cell line:</strong> The HEK293T-3HA-F508del-CFTR cell line is a modified HEK293T cell line that carries the F508del mutation in the CFTR gene, which is responsible for the most common mutation in cystic fibrosis. This mutation leads to a defective CFTR protein that impairs the normal function of the chloride channel. The cell line is therefore ideal for studying the effects of this mutation and for evaluating potential therapies for cystic fibrosis.
<br/><strong>CFBE41o- cell line:</strong> The CFBE41o- cell line, derived from the bronchial epithelial cells of a cystic fibrosis patient, is homozygous for the ΔF508-CFTR mutation and was essential for our cystic fibrosis research. . A reduced CFTR expression level is present. The cell line carries the CFTR defect and can therefore represent a patient with CF. The cell line is used to test our mechanism. These cells were immortalized with a replication-defective plasmid that retains their physiological properties.
</p>
<p>
<strong>HEK293T-3HA-F508del-CFTR cell line:</strong> The HEK293T-3HA-F508del-CFTR cell line is a modified HEK293T cell line that carries the F508del mutation in the CFTR gene, which is responsible for the most common mutation in cystic fibrosis. This mutation leads to a defective CFTR protein that impairs the normal function of the chloride channel. The cell line is therefore ideal for studying the effects of this mutation and for evaluating potential therapies for cystic fibrosis.
</p>
<p>
<strong>CFBE41o- cell line:</strong> The CFBE41o- cell line, derived from the bronchial epithelial cells of a cystic fibrosis patient, is homozygous for the ΔF508-CFTR mutation and was essential for our cystic fibrosis research. A reduced CFTR expression level is present. The cell line carries the CFTR defect and can therefore represent a patient with CF. The cell line is used to test our mechanism. These cells were immortalized with a replication-defective plasmid that retains their physiological properties.
When working with the HEK293T and CFBE41o- cell lines, it’s important to consider the minimal risks associated with their use. While not harmful on their own, the genetic modifications in HEK293T cells require careful handling to prevent accidental release or exposure. These cells, engineered to overexpress CFTR, including the F508del mutation, necessitate strict safety measures like regular monitoring and proper waste disposal to comply with S1 laboratory standards. Similarly, CFBE41o- cells, due to their genetic modifications and disease relevance, require careful handling to avoid cross-contamination and ensure biosafety.
</p>
<p>
<strong>Human nasal epithelial cells (hNECs):</strong> Human nasal epithelial cells (hNECs) were harvested using a nasal brush, a minimally invasive procedure, and cultured in air-liquid interface (ALI) cultures to model the airway epithelium. Human nasal epithelial cells (hNECs) were obtained using a nasal brush, a minimally invasive technique, and then cultured in air-liquid interface (ALI) cultures to model the airway epithelium. Using these primary cultures, derived from donors with airway diseases such as cystic fibrosis, we were able to simulate the in vivo conditions of such diseases.
<br/>Due to the sensitive nature of these primary human cells, we performed all experiments with hNECs in our S2 laboratory, where increased safety precautions were taken. This included strict safety controls, safe handling of samples and proper disposal of materials after testing. In particular, the hNECs underwent HHH (Triple H: HIV, HCV and HBV) testing to ensure that no contamination occurred during sample collection or experimentation. These tests included sterility testing, viability assessments and contamination testing to ensure the safety and integrity of both the samples and the laboratory environment. After a negative HHH test, the primary cultures can be treated as S1. In addition, the nasal epithelial cells were handled with the utmost care during collection, ensuring that all procedures were performed under sterile conditions to avoid any risk of contaminationFor this purpose, the intensive examination of ethical questions was fundamental and a constant companion of our project. The numerous results from the interviews in the areas of: Ethics, storage and training in the handling of samples have been summarized in a guideline for patient consent for Germany and are intended to provide iGEM teams with the scope, critical examination and observance of iGEM rules, international and national guidelines.
Due to the sensitive nature of these primary human cells, we performed all experiments with hNECs in our S2 laboratory, where increased safety precautions were taken. This included strict safety controls, safe handling of samples and proper disposal of materials after testing. In particular, the hNECs underwent HHH (Triple H: HIV, HCV and HBV) testing to ensure that no contamination occurred during sample collection or experimentation. These tests included sterility testing, viability assessments and contamination testing to ensure the safety and integrity of both the samples and the laboratory environment. After a negative HHH test, the primary cultures can be treated as S1. In addition, the nasal epithelial cells were handled with the utmost care during collection, ensuring that all procedures were performed under sterile conditions to avoid any risk of contaminationFor this purpose, the intensive examination of ethical questions was fundamental and a constant companion of our project. The numerous results from the interviews in the areas of: Ethics, storage and training in the handling of samples have been summarized in a guideline for patient consent for Germany and are intended to provide iGEM teams with the scope, critical examination and observance of iGEM rules, international and national guidelines.
</p>
<H4 text="Checkin for Delivery "></H4>
<p>
Our finished construct is designed to be delivered into the lung via an inhaler using lipid nanoparticles (LNPs). To be more spezific a selective organ-targeting (SORT)- LNPs were developed to deliver mRNA specifically to the lung, with special measures taken to increase biocompatibility and safety. Since the LNP composition is very specific and also differs from other formulas, we submitted the LNP as a checkin:
<br/><strong>LNP:</strong> These LNPs are then taken up by epithelial cells through endocytosis, releasing the construct into the cytosol. We carefully evaluated the potential risks, including unintended immune responses and the need for precise dosing to minimize side effects. In addition, we have conducted an in-depth analysis of the dual-use potential of our technology. Dual-use refers to the possibility that scientific advances can be used for both civilian and military purposes. Therefore, we have implemented strict safety protocols and ethical guidelines to ensure that our technology is used exclusively for peaceful and therapeutic applications.
</p>
<p>
<strong>LNP:</strong> These LNPs are then taken up by epithelial cells through endocytosis, releasing the construct into the cytosol. We carefully evaluated the potential risks, including unintended immune responses and the need for precise dosing to minimize side effects. In addition, we have conducted an in-depth analysis of the dual-use potential of our technology. Dual-use refers to the possibility that scientific advances can be used for both civilian and military purposes. Therefore, we have implemented strict safety protocols and ethical guidelines to ensure that our technology is used exclusively for peaceful and therapeutic applications.
</p>
</div>
</Section>
......@@ -64,10 +93,39 @@ export const Safety: React.FC = () =>{
</Section>
<Section title="Biosafety" id="Biosafety">
<Subesction title="Mechanism" id="Biosafety1">
<LoremMedium/>
<p>
The biosafety of our Prime Editing complex has been a top priority throughout the entire development process. We have therefore tried to optimise all parts that influence the biosecurity of our system as much as possible. To ensure maximum biosecurity, we have created and tested many designs, as well as extensively researched alternatives and/or additional elements that contribute to biosecurity.
</p>
<H4 text="PAM disrupt" ></H4>
<p>
A key safety mechanism incorporated in our design of the Prime Editing complex is the disruption of the PAM sequence. For the nickase enzyme to function properly, it must bind directly to the DNA strand, a process that is facilitated by the presence of a specific sequence called the PAM (Protospacer Adjacent Motif). This critical interaction occurs through the recognition of the PAM sequence by the nickase itself. To achieve PAM disruption, the pegRNA (prime editing guide RNA) is specifically designed in a way so that the PAM sequence is situated within the reverse transcription template (RTT) of the pegRNA. By introducing a silent mutation within the RT template into the PAM sequence. Therefore the PAM sequence is effectively eliminated after the gene editing process is successfully completed [1]. As a result of that, the PAM sequence is no longer present on the DNA strand, preventing the nickase from binding again at the same location. This reduction in repeated or undesired binding of the nickase enhances the safety of our prime editing complex, minimizing the risk of unintended edits or off-target effects in subsequent steps. Ultimately, this feature contributes very much to the overall safety and reliability of the prime editing process.
</p>
<H4 text="pegRNA design - Spacer"></H4>
<p>
Biosafety is also guaranteed by the careful selection of the spacer, which plays a critical role in guiding the complex to its intended target site [2]. To ensure both precision and safety, we meticulously chose and rigorously checked the spacer using the CRISPick software [3]. This allowed us to evaluate whether our Spacer would be likely to target other regions than our target site and therefore allowing us to analyse and predict potential off-target effects, ensuring that erroneous edits are minimised. By optimising the spacer selection, we have not only significantly enhanced the overall editing efficiency, striking a balance between precision and performance, but especially ensured the utmost accuracy in directing the Prime Editor, further contributing to the safety of the editing process. [Bild 1]
</p>
<H4 text="Riboswitch"></H4>
<p>
Riboswitches are segments of an RNA strand that bind to small molecules, causing them to change their secondary structure by forming hairpin structures. This process regulates gene expression at the translation level by preventing ribosomes from binding at the RBS and translating the coding region on the RNA strand. 0For our project we also considered an ion-sensitive riboswitch, specifically dependent on sodium ions (Na⁺), as a regulatory mechanism. The secondary structure of this riboswitch prevents the binding of ribosomes to the ribosome binding site (RBS) under normal conditions, thus inhibiting the translation of the subsequent mRNA. When sodium ions bind to the riboswitch, a structural change occurs, exposing the RBS, which allows for the translation of the mRNA and the production of our fusion protein which is the main component of our prime editing system and therefore of enormous importance for it to work [4]. In the context of the CFTR mutation and its effects on the cell, the elevated Na⁺ levels play a crucial role. Due to the dysfunctional CFTR channel, which fails to properly function as a chloride channel, the ENaC channel (epithelial sodium channel) becomes upregulated. This upregulation results in an increased transport of sodium ions into the cell, leading to a higher intracellular sodium concentration. This elevated Na⁺ concentration creates a specific ionic environment that could potentially be utilized to regulate our Prime-Editing complex in a targeted manner. Given these specific ionic changes in the cell, we could have a disease-specific regulation of our Prime-Editing system based on the ionic situation typical of this condition. However, despite the initial promise of this approach, after further research, we concluded that the riboswitch, even considering the ion levels within epithelial cells, is overall too nonspecific and therefore too unreliable as a regulatory mechanism. Although the ion levels in CFTR cells are much lower, there are still low concentrations of sodium ions, which can lead to the riboswitch not being completely switched off.
[Bild 2]
As a further approach to developing alternative riboswitch variants, we considered the possibility of an RNA-regulated riboswitch targeting the defective mRNA sequence of the genetically defective CFTR gene. The basic idea behind this concept was that the riboswitch specifically binds to a region on the CFTR mRNA containing the F508Δ mutation. This binding should induce a structural change in the riboswitch on our prime editing complex’s mRNA that ultimately leads to exposure of the RBS to allow translation of the downstream sequence. This mechanism would be designed to react specifically to the defective CFTR mRNA and only cause a change in the secondary structure in the presence of the specific mutation. The riboswitch could thus ensure selective and disease-specific activation of our prime editing complex, which would be of particular interest in the context of genetic diseases such as cystic fibrosis. However, we did not pursue this approach any further. A major reason for this was the lack of sufficient literature providing a sound scientific basis for this specific application of a riboswitch. In
addition, our research steered us in a different direction, particularly with regard to the alternative mechanism involving the XBP1 intron to regulate the prime editing system. This alternative seemed more promising and was based on an established regulatory mechanism that is triggered by cellular stress and specifically responds to misfolding processes.
</p>
<H4 text="XBP1 Intron"></H4>
<p>After extensive research, we discovered a regulatory system in eukaryotic cells, the XBP1 mechanism. The activation of XBP1 is an important mechanism that occurs as part of the Unfolded Protein Response (UPR), a cellular stress response triggered by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). The ER is a key cellular component responsible for protein folding and transport. When many misfolded proteins accumulate in the ER, a specific regulatory mechanism is activated to reduce the stress on the ER. XBP1 activation is controlled by a protein called IRE1α, which is embedded in the ER membrane. IRE1α acts as a sensor for protein misfolding stress in the ER. Once IRE1α detects misfolded proteins, it dimerizes and becomes activated through autophosphorylation. This activation switches on the endoribonuclease activity of IRE1α, which is a crucial step in the activation of XBP1. The mRNA for XBP1 is continuously transcribed in the nucleus and transported to the cytoplasm, where it contains an intron that is not normally spliced out. This intron contains a stop codon, preventing the translation of a functional XBP1 protein. However, when ER stress activates IRE1α, the endoribonuclease domain of IRE1α splices this intron out of the XBP1 mRNA. This is an unconventional splicing event, as it occurs in the cytoplasm rather than in the nucleus. Once the intron is removed, the spliced XBP1 mRNA can be translated into a functional XBP1 protein. This activated XBP1 acts as a transcription factor, turning on genes that increase the protein-folding capacity of the ER and promote the degradation of misfolded proteins. In this way, XBP1 helps the cell cope with ER stress and restore balance in the protein-folding process. Thus, this mechanism originally functions within the cell in the context of ER stress to maintain ER function when protein folding is disrupted. [5] [6] Our idea was therefore to integrate this intron into the mRNA encoding our prime-editing complex and thus use this mechanism to ensure that a functional prime editor is only synthesized when there is a high accumulation of misfolded proteins in the cell (similar to F508del). This would therefore represent an optimal safety aspect, as our fusion protein, which is essential for prime editing, cannot be fully synthesised as long as the genetic defect is not present in the cell. Accordingly, this provides the security that no healthy cells, as well as correctly edited cells, cannot be edited, which is an enormous contribution to biosafety. However, there was too much uncertainty about the extent to which other factors, such as misfolded proteins that are not associated with the CFTR protein, play a role in this mechanism. And since we could not and did not want to take the risk of such factors initiating the system, we decided against using it. To clarify this unknown correlation, we have considered a future experiment in which we want to switch this intron in front of a fluorescent marker and express it in cells with defective CFTR in order to confirm/investigate the dependence of intron splicing and the presence of CFTR F508del.</p>
</Subesction>
<Subesction title="Delivery" id="Biosafety2">
<LoremMedium/>
<Subesction title="Safety aspects of our Airbuddy" id="Biosafety2">
<H4 text="SORT LNP and Cytotoxicity"></H4>
<p>
We have carefully considered the biosafety aspects of our delivery system, starting with the decision between Adeno-associated viruses (AAV) or lipid nanoparticles (LNPs) as delivery systems. Our comparison revealed that the biocompatibility and safety of LNPs are paramount for our approach. That is why we chose selective organ-targeting (SORT) lipid nanoparticles (LNPs) [1] in the context of targeted pulmonary mRNA delivery. One of our primary concerns with the LNP was the potential cytotoxicity of polyethylene glycol (PEG), a common stabilizing agent in LNP formulations. Aware of the immune responses PEG can trigger, potentially leading to cytotoxicity [2], we aimed at optimizing its concentration in our SORT LNPs to minimize such reactions while maintaining therapeutic efficacy. By the use of low molecular weight PEG, we addressed this problem. To test weather our approach succeeded, we conducted MTT and proliferation assays to ensure that our LNP posed no cytotoxicity risks.
</p>
<H4 text="Precision of our SORT LNP"></H4>
<p>
To further improve safety, we focused on reducing off-target effects. By incorporating specific SORT molecules, such as permanently cationic lipids like DOTAP, we ensured that the nanoparticles are systematically directed to the lungs. This precise targeting is particularly beneficial for respiratory diseases, as it enhances therapeutic effectiveness while limiting the impact on non-target organs. Our outlook of antibody conjugation as surface modification of our LNP for cell type-specific delivery, more exactly club cells [3] and ionocytes [4] as CFTR-expressing lung epithelial cells, would round off this aspect.
</p>
<p>
In summary, our design strategy emphasizes both safety and efficacy. The careful optimization of components like PEG 2000 and the use of targeted delivery molecules allow SORT LNPs to deliver therapeutic agents directly to the lungs, reducing systemic exposure and minimizing side effects. This targeted approach ensures more effective treatments, especially for conditions requiring localized intervention.
</p>
</Subesction>
</Section>
<Section title="Biosecurity" id="Biosecurity">
......
src/data/drug-data.tsx
+ 39
− 8
View file @ 70347a62
......@@ -9,7 +9,7 @@ export interface DrugDatensatz {
interface example{
title: string,
text: string
text: Array<string>;
}
export const drugdata: (Array<DrugDatensatz>) = [
......@@ -20,26 +20,53 @@ export const drugdata: (Array<DrugDatensatz>) = [
examples: [
{
title: "",
text: ""
text: [""]
},
{
title: "",
text: "string"
text: ["string"]
},
]
},
{
//gibt 4 Modulator Beispiele
name: "Modulators",
picture: "...",
introduction: "CFTR modulators represent a significant advancement in CF treatment since they are small molecules improving the function of the defective CFTR protein in a mutation-specific way, which helps restore chloride ion transport across cell membranes. Notable pharmaceutical agents include Trikafta®, Symdeko®, Orkambi® and Kalydeco® [1]. These medications have been demonstrated to significantly improve lung function and reduce pulmonary exacerbations. However, they are expensive and may cause side effects such as liver enzyme elevations and cataracts in pediatric patients [2]. Furthermore, they are not suitable for all CF patients since only mutations which produce a CFTR channel can be supported by CFTR modulators, not those mutations which lead to a missing CFTR channel (knock out) [1], e.g. stop-mutations including p.Arg553Ter or p.Gly542Ter [3]. ",
examples: [
{
title: "Trikafta",
text: "Active ingredient(s): Combination of elexacaftor/tezacaftor/ivacaftor \n Indications: For CF patients aged 2 years and older with at least one F508del mutation à 85 % of CF patients \n Mechanism: Elexacaftor and tezacaftor act as correctors on misfolded CFTR and permit delivery to the cell surface, thereby improving the channel density at the plasma membrane, while ivacaftor as a potentiator acts on CFTR channels that have reached the cell surface and increase the gating and conductance of ions [5]. \n Administration: Oral tablets \n Approval: Approved by the EMA in 2020 "
text: ["Active ingredient(s): Combination of elexacaftor/tezacaftor/ivacaftor","Indications: For CF patients aged 2 years and older with at least one F508del mutation à 85 % of CF patients","Mechanism: Elexacaftor and tezacaftor act as correctors on misfolded CFTR and permit delivery to the cell surface, thereby improving the channel density at the plasma membrane, while ivacaftor as a potentiator acts on CFTR channels that have reached the cell surface and increase the gating and conductance of ions [5].","Administration: Oral tablets","Approval: Approved by the EMA in 2020 "]
},
{
title: "Symdeko",
text: "Active ingredient(s): Combination of tezacaftor and ivacaftor \n Indications: For CF patients aged 6 years and older with specific mutations in combination with F508del or with two copies of F508del mutation \n Mechanism: Tezacaftor acts as a corrector on misfolded CFTR and permit delivery to the cell surface, thereby improving the channel density at the plasma membrane, while ivacaftor as a potentiator acts on CFTR channels that have reached the cell surface and increase the gating and conductance of ions [5] \n Administration: Oral tablets \n Approval: Approved by the EMA in 2018"
text: ["Active ingredient(s): Combination of tezacaftor and ivacaftor","Indications: For CF patients aged 6 years and older with specific mutations in combination with F508del or with two copies of F508del mutation", "Mechanism: Tezacaftor acts as a corrector on misfolded CFTR and permit delivery to the cell surface, thereby improving the channel density at the plasma membrane, while ivacaftor as a potentiator acts on CFTR channels that have reached the cell surface and increase the gating and conductance of ions [5]", "Administration: Oral tablets", "Approval: Approved by the EMA in 2018"]
},
{
title: "Orkambi",
text: ["Active ingredient(s): Combination of lumacaftor and ivacaftor", "Indications: For CF patients aged 1 year and older with two copies of the F508del mutation","Mechanism: Lumacaftor acts as a corrector on misfolded CFTR and permit delivery to the cell surface, thereby improving the channel density at the plasma membrane, while ivacaftor as a potentiator act on CFTR channels that have reached the cell surface and increase the gating and conductance of ions [5]","Administration: Oral tablets","Approval: Approved by the EMA in 2015"]
},
{
title: "Kalydeco",
text: ["Active ingredient(s): Ivacaftor","Indications: For CF patients aged 4 months and older with a gating mutation in the CFTR gene (excluding F508del)","Mechanism: Ivacaftor as a potentiator acts on CFTR channels that have reached the cell surface and increase the gating and conductance of ions [5]","Administration: Oral tablets","Approval: Approved by the EMA in July 2012"]
},
]
},
{
name: "Mucolytics & inhalation",
picture: "...",
introduction: "",
examples: [
{
title: "",
text: ["test"]
},
{
title: "",
text: ["test2"]
},
{
title: "",
text: ["test2"]
},
]
},
......@@ -50,11 +77,15 @@ export const drugdata: (Array<DrugDatensatz>) = [
examples: [
{
title: "",
text: "test"
text: ["test"]
},
{
title: "",
text: ["test2"]
},
{
title: "",
text: "test2"
text: ["test2"]
},
]
}
......
src/data/hptimelinedata.tsx
+ 106
− 17
View file @ 70347a62
......@@ -116,21 +116,23 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
vorname: "Kristian",
nachnname: "Müller",
job: "Research Group Cellular and Molecular Biotechnology",
affiliation: "Technical Faculty of Bielefeld University",
pictureurl: pics['kristian'],
tag: "Academia",
heading: "",
heading: "Discussion about the delivery method- AVV vs. LNPs",
interviewtabid: "kristian",
cardtext: "",
language: "de",
quote: "",
aimofcontact: "",
insights: "",
implementation: "",
quote: "X",
aimofcontact: "X",
insights: "X",
implementation: "X",
},
{
vorname: "Max",
nachnname: "Beckmann",
job: "Bielefeld University",
affiliation: "Patient and Student of Bielefeld University",
pictureurl: pics['max'],
tag: "Patient",
heading: "Gathering valuable insights from the patient’s perspective",
......@@ -210,10 +212,10 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
<QaBox q="Do you think there has to be more effort concerning diagnostics?" a="Early diagnosis is covered by the screenings."/>
<QaBox q="Since you almost had to sue for your medication, do you know if there are any lawyers specializing in cases like this? " a="No, I don’t. "/>
<QaBox q="Are most of the other patients you know in good health like you?" a="No. Another boy my age got a fungal infection and does not have long time left to live. "/>
</>
</>,
},
{
title: "XXX",
title: "Prof. Dr.",
vorname: "Christoph",
nachnname: "Weber",
job: "",
......@@ -259,7 +261,6 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
language: "de",
quote: "",
aimofcontact: "",
insights: "",
implementation: "",
},
......@@ -293,6 +294,24 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
implementation: "",
type: "meta"
},
{
vorname: "Jan-Phillipp",
nachnname: "Gerhards",
job: "Student",
affiliation: "Intern at Harvard/ Boston Childrens Hospital",
pictureurl: pics['placeholder'],
tag: "Academia",
heading: "Discussion on optimizing our pegRNA Design to improve precision in prime editing",
interviewtabid: "JPpegRNA",
cardtext: "",
language: "de",
quoteNachname:"Lenger",
quoteVorname:"Malte",
quote: "The interview proved invaluable in gaining an initial understanding of the principles of pegRNA design and optimisation, particularly in the context of silent edits.",
aimofcontact: "The aim of the contact was to engage in a discussion about prime editing and pegRNAs, as the Jan-Phillip Gerhards had used these technologies in his internship. We sought to exchange ideas, gather insights, and explore potential improvements or strategies for our project, leveraging his experience with prime editing tools. His practical knowledge in this field was very valuable for refining our approach and ensuring we were aligned with the latest advancements and methodologies in prime editing. ",
insights: "During our discussion we gained valuable insights that had a significant impact on our project. One of the most important findings was the effectiveness of silent edits, which will enable us to make our PrimeGuide safer. Silent edits changes the sequence of bases in the DNA in such a way that the resulting protein remains unchanged, because the genetic code is redundant. This means that different codons can code for the same amino acid. By making silent edits in addition to correcting the CFTR gene, we can prevent the pegRNA from rebinding. We have also learned that the length of the primer binding site (PBS) plays a crucial role in determining optimal results and that it is recommended to keep the PBS temperature close to 37°C. Specifically, PBS lengths of 17nt (38.3°C) and 16nt (36.4°C) were found to be ideal options. For our planned set of 12 samples, it was recommended to use three different PBS lengths (differing by +/- 1nt from that close to 37°C) in combination with four RTTs to achieve the best result. Another important finding was the use of non-annotated regions with overhangs for cloning, which could give better results in our experiments. However, we also encountered concerns that circRNA, a covalently closed circular RNA molecule, might be sterically hindered by Cas9, which we need to investigate further. When discussing cloning overhangs, we learned that a base-pair length close to 60°C is optimal. However, the use of a 15nt PBS was not recommended as it has a lower temperature range which could affect performance. Although we still need to confirm the oligonucleotide delivery time, these findings will help us to refine our cloning strategy, optimise PBS selection and improve our overall approach to primer editing, especially in terms of the pegRNA design.",
implementation: "We incorporated the lessons learned from our discussions on prime editing and silent editing directly into our project by refining our approach to gene editing. Based on feedback about the optimal length of primer binding sequences (PBS) and RTTs, we adjusted the design of our pegRNAs to ensure greater precision and efficiency in our experiments. In particular, we learned that using PBS lengths close to 37°C melting temperatures (e.g. 16-17 nucleotides) increased stability, which led us to fine-tune these sequences for improved editing results. The concept of silent editing became an integral part of our safety strategy, allowing us to make changes to the DNA more precise. We also revised our cloning strategies by considering the appropriate overhang length, targeting a base pair length near the melting temperature of 60°C to improve cloning efficiency. We also reassessed the practicality of ordering shorter PBS sequences, concluding that lengths shorter than 15 nt were less advantageous due to reduced efficiency. By integrating these findings, we optimised our experimental workflow and made informed decisions about the tools and methods for our prime editing experiments. ",
},
{
vorname: "Katrin",
nachnname: "Westhoff",
......@@ -311,6 +330,7 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
pictureurl_interview: "https://static.igem.wiki/teams/5247/photos/hp/katrin-westhoff-zoom.webp",
},
{
title: "Dr.",
vorname: "Cristian-Gabriel",
nachnname: "Olariu",
job: "pediatrician",
......@@ -321,11 +341,78 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
interviewtabid: "olariu",
cardtext: "",
language: "de",
quote: "",
aimofcontact: "",
quote: "For most families, it’s a shock. Cystic fibrosis still has a strong association with being a life-threatening disease, despite the fact that we now have good treatments, and many patients can live healthy lives. The diagnosis puts a huge psychological strain on the family, especially when dealing with very young children.",
aimofcontact: "To gain a deeper insight into the path to diagnosis, we invited pediatrician Dr. Cristian-Gabriel Olariu from the University Department of Pediatrics and Adolescent Medicine to share his experiences with cystic fibrosis (CF) patients with us. We interviewed him because of his expertise in the effects of diagnosis on the patient and the family members, but also on daily life. Additionally, we want to close the gap and create a bridge between academic research and clinical applications. Therefore, Dr. Olariu gave insights about the clinical perspectives on CF patients." ,
insights: [<p>We invited Max, our CF patient contact, to join Dr. Olariu in discussing the intersection of academic research, clinical application, and patient needs. Through our connection with CF Vests Worldwide (link zu deren Website? https://www.cfvww.org), an organization dedicated to providing life-saving therapy vests to cystic fibrosis patients globally, we gained insights into the challenges faced by CF patients, particularly in regions like Thailand, where access to advanced treatments and medical devices is limited. The conversation highlighted the critical role of early diagnosis and intervention, as well as the quality-of-life challenges many patients endure due to conventional treatments that may not be effective for everyone. Innovative approaches, such as our SORT LNP (lipid nanoparticle) delivery system, present promising alternatives for CF therapy. This system, which allows for RNA encapsulation and administration via dry spray inhalation, could revolutionize treatment by targeting lung cells more effectively, particularly in resource-limited settings. Dr. Olariu underscored the need for psychological support and coordinated care for CF patients, emphasizing that novel therapies like LNP-based gene treatments have the potential to improve treatment efficacy and accessibility, ultimately reducing the lifelong burden of care for patients and their families. </p>,
<ol>
<li>Diagnosis:</li>
<li>Detection through newborn screening.</li>
<li>Further tests (including sweat tests) are conducted if results are abnormal.</li>
</ol>,
<ol>
<li>Early Treatment:</li>
<li>Begins with inhalations, physiotherapy, and medications.</li>
<li>Aim: Prevention of severe complications and organ protection.</li>
</ol>,
<ol>
<li>Challenges:</li>
<li>Some patients do not respond well to conventional treatments.</li>
<li>Significantly impacts quality of life.</li>
</ol>,
<ol>
<li>Family Burden:</li>
<li>Medical challenges create a significant burden.</li>
<li>Psychological stress due to lifelong treatment.</li>
</ol>,
<ol>
<li>Importance of Support: </li>
<li>Psychological support is crucial.</li>
<li>A well-functioning treatment team is essential.</li>
</ol>,
<p>We have jointly weighed up the extent to which an early diagnosis is always an advantage, as some parents perceive an early diagnosis as an additional burden and would prefer to experience the first years of their child's life without constant medical intervention. Especially when there are cases in which patients only show a clear clinical picture at an advanced age. The psychological burden also lies with the children, who often experience medical trauma because they are involved in such intensive medical care from birth. Additionally, the treatment of cystic fibrosis is very expensive, and the costs are covered by health insurance companies to varying degrees. In some countries, such as the USA, Ukraine or Developing countries, many families cannot afford the necessary treatments. Dr Olariu drew our attention to another problem in the treatment of cystic fibrosis. Infections, especially with bacteria such as Pseudomonas spcc., are difficult to treat and often lead to long hospital stays. Max, our patients’ representative, who knows Dr. Olariu through his treatment, talked about his infections with Pseudomonas spcc., illustrating the reality of an invisible danger that determines a patient's everyday life. Strict hygiene measures are required to prevent infections, such as wearing face masks in hospital and careful handling of potential sources of infection. The clinics where cystic fibrosis patients are treated work closely with a multidisciplinary team of doctors, psychologists, physiotherapists and nutritionists to ensure that patients receive holistic care. At the same time, research is constantly being carried out and new therapeutic approaches developed, such as the use of nanoparticles to improve drug delivery. Former patients are also involved in research and provide valuable insights and advances. </p>
,<ol>
<li>Pros of Early Diagnosis and Treatment</li>
<ol>
<li>Timely Intervention: Prevents severe organ damage and improves long-term outcomes.</li>
<li>Holistic Care: Involves a multidisciplinary team for comprehensive patient support.</li>
<li>Access to Innovations: Allows patients to benefit from advancements like nanoparticle drug delivery.</li>
<li>Family Support: Provides education and resources for effective management from the start.</li>
</ol>
</ol>,
insights: "",
implementation: "",
<ol>
<li>Cons of Early Diagnosis and Treatment</li>
<ol>
<li>Psychological Burden: May cause stress for parents and children due to constant medical interventions.</li>
<li>Cost Implications: Treatments can be expensive, with varying insurance coverage, leaving many families unable to afford care.</li>
<li>Infection Risks: Patients still face risks from infections like Pseudomonas spp., leading to potential hospitalizations.</li>
<li>Over-medicalization: Continuous focus on treatment can overwhelm families, affecting the quality of early childhood experiences.</li>
</ol>
</ol>
],
implementation: "In summary, our project greatly benefited from the conversation with Dr. Olariu. His insights into the complexities of cystic fibrosis treatment, particularly the significance of early diagnosis, were invaluable. Max’s personal experiences added a crucial human perspective, illustrating the medical and psychological challenges he faces, including infections with Pseudomonas spp. Dr. Olariu emphasized the importance of a multidisciplinary approach, involving not just medical professionals but also psychologists, physiotherapists, and nutritionists for holistic care. This discussion helped us appreciate the balance between timely interventions and the emotional burden on patients and their families, guiding us to develop a more empathetic understanding of living with cystic fibrosis. ",
interview: <>
<QaBox q="Could you please tell us about the journey that parents go through with their CF-sick children from the first visit to diagnosis and treatment?" a="Since 2016, cystic fibrosis (CF) diagnosis has been part of newborn screening. This means that we receive many children right after birth whose screening results were abnormal. These children are then sent to us for further clarification. Not every child with an abnormal screening result is sick, so we perform a sweat test, and about one-third of the children are diagnosed with the disease. The advantage of early diagnosis is that we can intervene and start treatment early to prevent organ damage. However, there are also rare mutations where the course of the disease is difficult to predict." />
<QaBox q="What are the pros and cons of newborn screening for cystic fibrosis?" a="From a medical point of view, it’s beneficial that we can catch many of these cases early, allowing us to act swiftly. There are even medications for small babies, and early intervention can protect organs, preventing conditions that would require transplants later on. On the downside, because of the wide variety of genetic mutations, some cases we identify may not show significant symptoms until adulthood. This creates a dilemma, as we can’t predict how their condition will progress, but we still start treatments early, which can be stressful for families." />
<QaBox q="Can you give us an example of how this stress impacts families?" a="Yes, I’ve been caring for a patient from birth who is now five years old and doing very well. However, from the beginning, she had to undergo physiotherapy, regular check-ups, and blood tests, even though she hasn’t shown any major symptoms. Her mother once told me she wasn't sure if she would make the same decision again, as the early intervention caused a lot of stress. She wondered if she might have enjoyed the first year of her child’s life more if things had been more relaxed. Now, at age five, nothing significant has changed in her condition, and they’ve decided against starting modulator therapy for the time being." />
<QaBox q="How do families typically react when a CF diagnosis is confirmed?" a="For most families, it’s a shock. Cystic fibrosis still has a strong association with being a life-threatening disease, despite the fact that we now have good treatments and many patients can live healthy lives. The diagnosis puts a huge psychological strain on the family, especially when dealing with very young children. The most important factor in managing this, aside from medical treatments, is the support from the medical team. It’s critical to have a team that works well together, not just a single doctor calling all the shots. Families often need much more psychological and nutritional support early on than medical intervention, and this is where having a multidisciplinary team becomes essential." />
<QaBox q="What is the process for diagnosing and treating older patients who haven’t been through newborn screening?" a="Older patients who come to us with complaints may not have undergone newborn screening, so they are diagnosed based on their symptoms. These complaints can range from mild to severe and are often non-specific, like chronic cough or failure to thrive. When the cause of these symptoms isn’t immediately clear, we do a sweat test. Once diagnosed, we can start treatment, which often involves working with a psychologist to help the family process the news." />
<QaBox q="How do you support families during the initial shock of diagnosis?" a="When the diagnosis is particularly difficult for families to process, we sometimes have the patients stay in the hospital for up to a week. This gives us time to meet with them daily, answer questions, and provide guidance. During the first consultation, families often fall into a state of shock, and no matter how carefully the doctor explains things, it’s hard for them to absorb all the information. Meeting with them again over the following days helps, and we have specialists in hygiene, physiotherapy, and social counseling on the team to offer holistic support." />
<QaBox q="What happens if a child gets infected with Pseudomonas or another bacterial culture in the lungs?" a="Pseudomonas is one of the most feared infections for CF patients. It’s a common environmental bacterium that is difficult for CF patients to clear from their lungs. Once we detect it, we treat the patient with specific antibiotics, often through intravenous delivery over two weeks in the hospital. After the initial treatment, patients may continue with inhaled antibiotics for several months to prevent further infection. It’s a very intensive process, taking a lot of time and energy, and even though we may get rid of the infection a few times, eventually the germ can become resistant and stay in the body." />
<QaBox q="Are there any preventative measures to avoid Pseudomonas infection?" a="Yes, there are hygiene measures. For example, CF patients always wear masks in the hospital to avoid infection from other patients. But it’s difficult to avoid Pseudomonas entirely since it’s found in stagnant water and other places in the environment. We advise patients to be cautious with water sources like sinks or ponds. However, we need to balance strict hygiene with quality of life, especially for children, as being overly strict can lead to obsessive-compulsive behaviors without necessarily reducing the risk of infection." />
<QaBox q="Do some families resist the medical advice on preventing infections?" a="On an emotional level, I feel that families who take calculated risks to improve their quality of life tend to cope better. Overprotection can lead to greater psychological stress. However, I don't have enough experience to say for sure whether those who don’t protect themselves as strictly get infected earlier or suffer worse outcomes. It’s also worth noting that new therapies are now available that help reduce infection risks, allowing for a bit more freedom, especially for children." />
<QaBox q="How often do patients need to be tested for infections like Pseudomonas?" a="The official guideline is every two months, but realistically we aim for every 3-4 months. Regular testing is important because Pseudomonas can be present without symptoms. If too much time passes before detection, it becomes harder to remove the infection." />
<QaBox q="How do you manage chronically infected patients?" a="Patients who are chronically infected with Pseudomonas don't stay in the hospital indefinitely. They usually remain at home, inhaling antibiotics daily and taking physiotherapy to help clear mucus from their lungs. Intravenous antibiotic therapy is reserved for more severe cases or during clinical deterioration." />
<QaBox q="Are chronically infected patients allowed to visit your practice?" a="Yes, chronically infected patients are allowed to visit the practice. We try to schedule them at different times to avoid contact between infected and non-infected patients, and we often use separate rooms to minimize risk." />
<QaBox q="How often do children and adults need to have lung function tests?" a="You can’t conduct a good lung function test until the child is around five years old. After that, it becomes part of the routine check-up because it’s non-invasive and provides a good indicator of lung health. We see children every three months, and I believe the protocol is the same for adults." />
<QaBox q="What do you think about support groups or health retreats for CF patients?" a="Support groups are extremely important. Although we are a good medical team, advice from peers often resonates more with patients. We’ve organized two parents' evenings recently, where parents can exchange experiences and support each other. Unfortunately, we can’t invite the children themselves due to the risk of infection, but in rehabilitation settings, they can meet in germ-specific groups and benefit from shared experiences." />
<QaBox q="Is there a risk of antibiotic resistance with repeated treatments?" a="Yes, resistance is a concern, especially with repeated antibiotic treatments. However, there’s often a discrepancy between what we see in lab tests and the clinical outcomes. Even if a germ shows resistance on paper, many patients still respond well to treatment. We base our decisions more on clinical outcomes than lab results, changing antibiotics only if the patient’s condition doesn’t improve." />
<QaBox q="Are there any side effects to the medications?" a="Yes, all medications have potential side effects, though many of them are minor, like rashes or stomachaches. One serious side effect of some antibiotics is hearing damage, which can lead to lifelong hearing loss. This is why we closely monitor patients in the hospital when starting treatments. The newer therapies, like modulators, can cause liver stress, so we regularly check liver enzymes in the blood. However, severe side effects are rare, and the drugs are generally well tolerated." />
</>
},
{
vorname: "Mattijs",
......@@ -338,11 +425,13 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
interviewtabid: "mattijsinv",
cardtext: "",
language: "en",
quote: "",
aimofcontact: "",
insights: "",
implementation: "",
quote: "I believe the challenge lies in the process when your cell has to repair the new DNA strand",
aimofcontact: "Shortly after we decided to use prime editing as the gene editing method for our cystic fibrosis therapy, Mattijs Bulcaen from the Laboratory of Molecular Virology and Gene Therapy at KU Leuven and his colleagues published a paper directly related to our research1. In contrast to our approach, Bulcaen et al. 2024 targeted other, less common but drug-refractory CFTR-specific mutations (L227R- and N1303K). ",
insights: "The insights gained from this interview proved invaluable in shaping our subsequent mechanistic approaches. Besides his comprehensive perspective of the significant advancements in the field of prime editing, Mattijs engaged us in a constructive dialogue, offering a critical assessment of our own ideas and approaches. ",
implementation: "Mattijs explained why he did not try to target F508del. Of all the possible applications of Prime Editing in gene therapy, he told us, the CFTR F508del mutation is the most obvious target, but no substantial editing efficiency could be achieved at this target yet. He further elaborated that this might be due to DNA packaging, low cutting efficiencies at that locus, the AT rich region surrounding F508del and also possible intramolecular binding of the pegRNA, but we do not really understand the mechanistic reason yet. Additionally, he mentioned a talk given by David Liu,[Link] the principal investigator behind prime editing that helped us to consider further novel advancements in F508del-specific CFTR-treatment and include them into our project. Beside the clinical context, we discussed different methods of testing edited cells for CFTR reconstitution, such as measurements using the Ussing chamber, organoid swelling assays and halide sensitive eYFP fluorescence assays. Additionally, we discussed the use of stem loops for protection of the pegRNA, which we then included into our own pegRNA design. Lastly, we officially cooperated with the research group and the university: Mattijs was willing to share two different HEK293T cell lines [Link] stably overexpressing the CFTR wild-type and F508del proteins. We also visited Mattijs in his laboratory in Leuven to discuss this further. During our visit we discussed different downstream applications on proteomic, genomic and electrophysiological levels. Besides antibody staining of the CFTR-3HA protein, we asked for his insights on patch clamp measurements and DNA sequencing as well as the advantages and disadvantages of different delivery systems for prime editors. Additionally, Mattijs provided more details into the CFTR overexpressing cell lines, and we received guidance on handling of these kinds of cells. Until the end of the project, we maintained communication with Mattijs Bulcaen via email for further questions and gave updates concerning our project to implement the feedback loop according to our integrated Human Practice Framework.",
/* references:
<ol>
/*<!-- Citation num 1--> */
},
{
vorname: "Nicole",
......
src/data/steckbriefe.ts
+ 2
− 2
View file @ 70347a62
......@@ -917,7 +917,7 @@ export const pis: Array<SteckbriefInterface> = [
pronouns: "he/him",
studiengang: "Research Group Leader - Molecular and Cellular Biotechnology",
headof: "Second Principle Investigator",
igemjob: ["Technical Facility of Bielefeld University"],
igemjob: ["Technical Faculty, Bielefeld University"],
whyigem: [
"The combination of fun and progress",
],
......@@ -931,7 +931,7 @@ export const pis: Array<SteckbriefInterface> = [
"iGEMmer since 2007 and keeping it rolling (any resemblance to Sisyphus is purely coincidental)",
],
favlabmusic: "Sam Cooke - Wonderful World",
scientificinterests: "Genomcis, Cloning Strategies and Adeno Associated Viruses",
scientificinterests: "synthetic biology, gene and protein design, gene therapy, adeno-associated virus",
islands: "",
onechange: "",
hobbies: []
......
src/data/symptom-data.tsx
+ 17
− 17
View file @ 70347a62
......@@ -9,7 +9,7 @@ export interface SymptomDatensatz {
interface example{
title: string,
text: string
text: Array<string>;
}
export const symptomdata: (Array<SymptomDatensatz>) = [
{
......@@ -19,11 +19,11 @@ export const symptomdata: (Array<SymptomDatensatz>) = [
subsections: [
{
title: "",
text: "string"
text: ["string"]
},
{
title: "",
text: "string"
text: ["string"]
},
]
},
......@@ -34,11 +34,11 @@ export const symptomdata: (Array<SymptomDatensatz>) = [
subsections: [
{
title: "",
text: "string"
text: ["string"]
},
{
title: "",
text: "string"
text: ["string"]
},
]
},
......@@ -49,11 +49,11 @@ export const symptomdata: (Array<SymptomDatensatz>) = [
subsections: [
{
title: "",
text: "string"
text: ["string"]
},
{
title: "",
text: "string"
text: ["string"]
},
]
},
......@@ -64,11 +64,11 @@ export const symptomdata: (Array<SymptomDatensatz>) = [
subsections: [
{
title: "",
text: "string"
text: ["string"]
},
{
title: "",
text: "string"
text: ["string"]
},
]
},
......@@ -79,11 +79,11 @@ export const symptomdata: (Array<SymptomDatensatz>) = [
subsections: [
{
title: "",
text: "string"
text: ["string"]
},
{
title: "",
text: "string"
text: ["string"]
},
]
},
......@@ -94,11 +94,11 @@ export const symptomdata: (Array<SymptomDatensatz>) = [
subsections: [
{
title: "",
text: "string"
text: ["string"]
},
{
title: "",
text: "string"
text: ["string"]
},
]
},
......@@ -109,11 +109,11 @@ export const symptomdata: (Array<SymptomDatensatz>) = [
subsections: [
{
title: "",
text: "string"
text: ["string"]
},
{
title: "",
text: "string"
text: ["string"]
},
]
},
......@@ -124,11 +124,11 @@ export const symptomdata: (Array<SymptomDatensatz>) = [
subsections: [
{
title: "",
text: "string"
text: ["string"]
},
{
title: "",
text: "string"
text: ["string"]
},
]
}
......
src/sidebars/hpS.tsx
+ 1
− 0
View file @ 70347a62
......@@ -12,6 +12,7 @@ export function HpSidebar(){
}
const tabs = [
{tab: "Abstract"},
{ tab: "Overview" },
{tab: "Introduction"},
{tab: "Integrated Human Practices", subtabs: ["Framework", "Timeline", "Implementation", "Feedback", "Conclusion"]},
......
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