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Commit 720bc9df authored by Anurag Sarkar's avatar Anurag Sarkar
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IHP added

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......@@ -124,6 +124,60 @@ def edublog(blog):
# Render the edublog.html template and pass the individual blog content
return render_template(str(Path('pages')) + '/' + 'edublog.html', blog=readedublog(blog))
def listihpblogs():
# Traverse the edubloglist directory
filenames = next(walk('./wiki/ihpblogposts/'), (None, None, []))[2]
# Remove the ".md" extension
for i in range(len(filenames)):
filenames[i] = filenames[i][:-3]
ihpbloglist = {}
# Extract metadata from each Markdown file
for filename in filenames:
with open(f'./wiki/ihpblogposts/{filename}.md', 'r', encoding = 'utf-8') as file:
try:
ihpbloglist[filename] = markdown2.markdown(file.read(), extras=[
"metadata",
]).metadata
except:
ihpbloglist[filename] = "No Metadata"
return ihpbloglist
@app.route('/ihp')
def ihpbloglist():
# Render the edubloglist.html template and pass the list of educational blogs
return render_template(str(Path('pages')) + '/' + 'ihp.html', ihpbloglist=listihpblogs())
def readihpblog(blog):
# Read the individual educational blog file and convert it to HTML
try:
with open(f'./wiki/ihpblogposts/{blog}.md', 'r', encoding = 'utf-8') as file:
return markdown2.markdown(file.read(), extras=[
"code-friendly",
"fenced-code-blocks",
"tables",
"wiki-tables",
"strike",
"footnotes",
"break-on-backslash",
"metadata",
"target-blank-links",
"numbering",
"tag-friendly",
"cuddled-lists",
"latex",
])
except FileNotFoundError:
return 'IHP Blog Not Found'
@app.route('/ihpblogs/<blog>')
def ihpblog(blog):
# Render the ihpblog.html template and pass the individual blog content
return render_template(str(Path('pages')) + '/' + 'ihpblog.html', blog = readihpblog(blog))
def readnote():
try:
......
---
title: Aptaloop- iGEM DTU Denmark
author: Suvam Saswat Das
---
Further down the line, we discovered a software, **AptaLoop,** that had designed by **DTU, Denmark’s 2023 iGEM team.** Upon looking into the software and testing it, our team chanced upon a bug. In order to resolve the issue, and with the hope to expand our usage of the software further, our team had a meeting with one of DTU Denmark’s 2023 team members, Anu Oswal. She gave us inputs on using MAWS and on modifying the pipeline.
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---
title: PROTAC and Phosphomimetics
author: Suvam Saswat Das
---
Our co-Leader, Suvam, had a chance to meet **Prof. Ranabir Das**, and **Anindita Puri, NCBS**, who provided their inputs on PROTAC. They gave us insights on types of ligands and protein purification processes.
With the progress of time, we came across the concept of phosphomimetics. To understand this concept better, we consulted Surabhi Chandra, PhD, Prof. Hussain’s lab, and Shrivallabh Deshpande, PhD, Prof. Nair’s lab, who suggested that we give it a shot.
To seek expert opinion, we approached Prof. Muddashetty, who redirected us to **Prof. Sivaprakasam Ramamoorthy**.Prof. Ramamoorthy was not convinced of whether phosphomimetics would work for our system and suggested that we try it or consult a biochemist. He also provided many insights about tauopathies, and about the industries related to them. He also put forward the question of competing with large scale biotech giants and suggested that we should reform our research in order to make it marketable. He keenly listened our plan of action and participated in improving it. That short meeting changed many non-research aspects of our work.
To learn more about phosphomimetics, we approached **Prof. Saravanan Palani**, Biochemistry, IISc. He suggested that we try phosphomimetics, by switching out threonine or serine with aspartic acid or glutamic acid, in different combinations. He suggested that we check the phosphomimetic tau using molecular simulation and compare it with tau phosphorylated in the human body. He gave us insights into phosphomimetics and how we could test the similarity of a phosphomimetic and phosphorylated protein using spectroscopic techniques.
For further information, we approached to Paulomi Sanyal, PhD, **Prof. Ashok Sekhar’s** lab, Molecular Biophysics Unit, IISc, who works on phosphomimetics and the changes involved. She gave us first-hand information about how she employs it in her work and how we could incorporate it in ours. She also helped us design the phosphomimetic plasmid.
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---
title: iGEM Mentor- Dr. Roghaiyeh Safari
author: Suvam Saswat Das
---
We also had meetings with our iGEM mentor, Dr. Roghaiyeh Safari, Imperial College, London. She enquired about our business models, along with our idea and implementation. Her valuable feedback on business models and our pitch deck was utilised in our design. She did provoke our thoughts about the market and entrepreneurship. She also helped review our pitch decks and plan of action.
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---
title: Brain Health and Ageing Conference
author: Suvam Saswat Das
---
On 6 September 2024, a conference on Brain Health and Ageing was organised within the IISc campus. At this conference, our co-Leader Suvam, met **Prof. Henrik Zetterberg and Dr. Andrew Morris**, from HDR UK.
Prof. Zetterberg was quite impressed with our idea, and discussed how we could integrate our aptamer with diagnostics and have an effective treatment of Alzheimer’s Disease or other tauopathies, in the future. He also asked us to look upon new diagnostic molecules and if we could integrate them into our work. Dr. Morris shared his experience on the difficulty of predicting the epidemiological presence of Alzheimer’s. He also discussed about probable methods of enhancing the process.
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---
title: Speaking to the Public
author: Suvam Saswat Das
---
Along with scientifically maturing our idea, our team also focused on knowing real world issues and awareness among people. For this, our team visited doctors, conducted surveys among people and also looked upon the people who served as caregivers, both professional and family members, to the affected.
During one public survey session on the streets of Bangalore, we were keen to know about the awareness of people, and how well they know about dementia and AD. Our team found out that several people don’t even know that AD is prevalent in our country, and they just assume dementia to be a natural consequence of normal ageing. With this, we realised that there is a lot more to do in terms of awareness. People need to be educated about dementia, ageing and Alzheimer’s, and only then can we think of explaining our work and its importance to the common public.
We also had an indirect public response regarding these matters during IISc's Open Day. We had a diverse crowd, ranging from people who could delve into the molecularity of our work and its effects, whereas some people who were unaware that AD is not just a simple dementia. This was a small representation of the range of awareness and how we need to adapt in order to reach a larger audience and create an impact. We received important feedback from visitors, both scientific and societal.
In order to receive first-hand information and experience dealing with affected people, our teammates went to meet doctors and staff. Shouvik and Shripad visited **Dr. R. Umashankar** at the Bangalore Neuro Centre, for knowing his expertise and experience in this area. We were able understand the seriousness of this issue, especially when AD affects movement. Caregivers and families run through a state of turmoil and have a constant mental stress, which sometimes deteriorates their health too. The professionals also provided us with feedback on our idea, and aspects we should consider to work upon in the future.
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---
title: The All India iGEM Meet
author: Suvam Saswat Das
---
The All India iGEM Meet was like a mini Jamboree, and during the judging session, Dr. Lavanya Bhagavatula, Prof. R. Selvi Bharathavikru, Dr. Preeti Srivastava, Dr. Onkar Date and Dr. Shruti Sridhar reviewed our progress. They had an overall positive feedback, but also pointed out certain points on which we could improve, and suggested efficient ways to do so.
They advised us to review the situation of Alzheimer's and dementia in India, and look deeper into the existing myths and misconceptions, as well as social stigma, in society. They encouraged us to increase collaborations with R&D industries, as a lot of work is already being done on aptamers and their commercialisation. They also suggested how we can reach a wider public, and also how we can make a successful business model out of our project.
The judges mentioned that our proposed methodology put them in mind of many diseases which could be cured in a similar way, and hence recommended that we widen our scope and horizons. They appreciated our decision to switch our track from Therapeutics to Foundational Advance, and wished us luck for the Grand Jamboree.
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---
title: Meeting Prof. Varadarajan
author: Suvam Saswat Das
---
**Prof. Raghavan Varadarajan,** a researcher at the Molecular Biophysics Unit, IISc, was the first stakeholder and expert we consulted. At the time of our first meeting, we were still ideating and were completely new to the concept of using oligonucleotides for targeted protein degradation, having with ourselves nothing but a mere idea.
We intended, through our discussion with Prof. Varadarajan, to enhance our knowledge and learn more about this concept. The discussion helped us become confident in our idea and become convinced that we could pitch it as a certified model. It was then that we set off on a search to find a model disease, which we could work on, one that was widespread across the world - so that we might easily pitch it to people, and so that people would also relate to it.
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---
title: Meeting Prof. Mudashetty and Neuroscientists
author: Suvam Saswat Das
---
Having initially finalised on using **Alzheimer’s Disease (AD)** as a model, we found it incumbent to consult a neuroscientist for further guidance during our project. **Prof. Ravi Muddashetty**, from the Centre for Brain Research, IISc, was the first neuroscientist we consulted. Upon hearing our proposal, he gave us positive feedback about the basic idea, but also mentioned that the model disease which we had narrowed down on would be challenging to work on.
The presence of amyloids and its seeding properties make Alzheimer's a complex misfolded protein disease. He suggested that we look upon other diseases such as Huntington’s disease, Parkinson’s disease, tauopathies and Amyotrophic lateral sclerosis among others. Taking his valuable inputs and suggestions into consideration, we started reading about other diseases, their progression, molecularity and other characteristics. After deliberating debates, frequent consultations and umpteen rounds of meetings, we came to the decision of working on tauopathies as our model disease.
We also consulted other distinguished neuroscientists such as Prof. Giriraj Sahu and Prof. Rishikesh Narayanan, Molecular Biophysics Unit, IISc. Though their work did not directly pertain to AD, they could still provide positive feedback about our idea. Both referred us to an expert in Alzheimer’s and cellular neuroscience, Prof. Deepak Nair.
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---
title: Enter Our PI- Prof. Deepak Nair
author: Suvam Saswat Das
---
**Prof. Deepak Kumaran Nair,** Centre for Neuroscience, IISc, is an expert who has formerly worked upon Alzheimer’s Disease. Some of the students in his lab continue to work on projects related to AD. Upon hearing our idea and the rough plan of action, he provided us with positive feedback, and guidance on how we should progress. Prof. Nair even volunteered, with utmost excitement, to provide us with a mouse to carry out experiments on! It was unfortunate that we could not use it due to iGEM guidelines.
It was much to our honour that, over the course of time, Prof. Deepak Nair agreed to become the **principal investigator** for our project.
\ No newline at end of file
---
title: Aptamers and SELEX - Prof. Rahul Roy
author: Suvam Saswat Das
---
Shifting gears to the second component of our idea -- aptamers. Initially, we faced great difficulty in finding experts on aptamers within in our reach. After deliberate search and consultation, we came to learn that **Prof. Rahul Roy**, Dept. of Chemical Engineering, uses aptamers to create biosensors and devices.
Without further ado, we consulted him about aptamers, seeking suggestions on how we might proceed with it. Prof. Rahul Roy suggested that we use DNA-based aptamers, due to their stability and ease of handling. He also suggested that we look for a time-efficient way of performing SELEX, as conventional SELEX would not fit into our timeframe. This encouraged us to look for new protocols, and modified SELEX methods.
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---
title: Prof. T. Govindaraju
author: Suvam Saswat Das
---
While the planning of experiments was going on, Anurag and Avani came across **Prof. T. Govindaraju,** Bioorganic Chemistry, JNCASR, who had come for a conference. He was excited upon knowing about our idea. He gave details about Alzheimer's Disease, especially about aggregation and plaque formation. He also appraised us about some statistics of AD, and how the patient’s quality of life becomes. Moreover, he suggested for us to look upon diagnostic aspects alongside our work.
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---
title: Protein Phosphorylation- Prof. Tanweer Hussain
author: Suvam Saswat Das
---
A major part of our work involved direct use of our target protein molecule, the Tau protein. We had planned to produce the protein ourselves. With protein production out of the way, the big challenge that remained was its phosphorylation, the post-translational modification of the Tau protein.
To resolve this issue, we consulted a molecular biologist, **Prof. Tanweer Hussain**, Developmental Biology and Genetics, IISc. Prof. Hussain, who is closely associated with Nobel Laureate Prof. Venkatraman Ramakrishnan, is a pioneer in the field of RNA biology. Upon consultation, we came to learn about the difficulty and the necessity of experience for mammalian expression of protein.
After a series of consecutive discussion with Prof. Varadarajan and Prof. Hussain, we decided to use a bacterial model for protein expression and phosphorylate the purified protein in-vitro.
\ No newline at end of file
---
title: Meeting iGEM OLM Madrid
author: Suvam Saswat Das
---
While sifting through different protocols and newer systems of SELEX, we chanced upon the work of an iGEM team, OLM Madrid, that had tried to develop a more efficient system of SELEX. We consulted **Laura Armero Hernandez** from their team.
The meeting (facilitated via an online platform) provided many insights about SELEX, how tedious it can be, and the effectiveness of the result it provides. The method they used also took around 3-4 months to produce an effective and more selective aptamer. Considering the time constraint and our plan of action, Laura suggested that we avoid performing SELEX (since it was not the central feature of our idea but only a part of it). She instead encouraged us to use pseudo-SELEX or directly use an established aptamer.
\ No newline at end of file
---
title: Dr Ramalingam, Dr Bellier and Dr Liu
author: Suvam Saswat Das
---
We had series of discussions and deliberations with Prof. Nair to understand how we could modify the aptamer and enhance its selectivity to certain region. We also finalized our site of choice, 231-Threonine in phosphorylated Tau441. During these set of discussion, Prof. Nair suggested that we seek information from an expert. He connected us with one of his colleagues, **Dr. Nagendran Ramalingam,** from Brigham and Women's Hospital, Harvard Medical School.
Dr. Nagendran Ramalingam was so excited upon hearing the idea that he invited his colleagues **Prof. Jean-Pierre Bellier** and **Prof. Lei Liu,** of Brigham and Women's Hospital, Harvard Medical School. They too shared much enthusiasm about the idea and were positive about its outcomes. However, they were sceptical about certain points and raised their concerns about the difficulties they believed we would face.
The idea of phosphorylation, though could be used, was to be carefully planned and executed. Prof. Liu had the same opinion as most others we consulted about the process of SELEX, given the time constraint. From the meeting we received valuable inputs regarding phosphorylation, cell health assay and pseudo-SELEX process among others.
Halfway through our work, we had another meeting to update Dr. Ramalingam and his colleagues about the progress and received feedback for the same. They did help us plan our work efficiently, and also provided us with suggestions on testing and finalization of our aptamer.
---
title: Error Prone PCR
author: Suvam Saswat Das
---
More discussions with Prof. Varadarajan regarding cell-free systems for protein synthesis, and its short-comings followed. We also investigated the possibility of performing post-translational modifications using such systems. We had discussions about **Error-Prone PCR** and how we could efficiently increase its productivity. Debarghya and Manish, students from Prof. Varadarajan’s lab, also provided their inputs and insights regarding these topics.
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---
title: Meeting with Students from IIT Delhi
author: Suvam Saswat Das
---
Running parallel to the meetings and discussions about work in the wet lab, we were also making considerably progress in planning dry lab activities. We had a meeting with **ex-iGEMers from IIT Delhi,** who had developed pipelines and console for simulation and predictors. Since the two projects did not align much, we could not collaborate with them further. They, however, did provide valuable information and suggestions related to dry lab work, such as protein simulation and molecular modelling, among others, during the meeting.
\ No newline at end of file
......@@ -4,8 +4,19 @@
{% block lead %}{{ blog.metadata['author'] }} | {{ blog.metadata['date'] }}{% endblock %}
{% block backlink %}<a href="{{ url_for('bloglist') }}" class="text-white">Back to Blog List</a>{% endblock %}
{% block page_content %}
<link href="{{ url_for('static', filename = 'blog.css') }}" rel="stylesheet">
<div class="container">
<h1 class="text-center display-4">{{ blog.metadata.title }}</h1>
<p class="text-muted text-center">By {{ blog.metadata.author }} | {{ blog.metadata.date }}</p>
<link href="{{ url_for('static', filename = 'blog.css') }}" rel="stylesheet">
<p class="body-text">{{ blog|safe }}</p>
<a href="{{ url_for('pages', page='bloglist') }}">Back</a>
<div style="height: 10rem;"></div>
<a href="{{ url_for('pages', page='bloglist') }}">Back</a>
<div style="height: 10rem;"></div>
</div>
{% endblock %}
{% extends "layout.html" %}
{% block title %}iHP{% endblock %}
{% block lead %}Integrated Human Practices of iGEM IISc-Bengaluru{% endblock %}
{% block title %}IHP Blogposts{% endblock %}
{% block lead %}Browse through IHP posts.{% endblock %}
{% block page_content %}
<style>
p {
text-align: justify;
}
.section-title {
margin-top: 2rem;
margin-bottom: 1rem;
}
.subsection-title {
margin-top: 1.5rem;
margin-bottom: 0.75rem;
}
@media (max-width: 768px) {
h1 {
font-size: 1.75rem;
}
h2 {
font-size: 1.5rem;
}
h4 {
font-size: 1.25rem;
}
}
</style>
<div class="container mt-4 text-center">
<div class="row justify-content-center">
<div class="col-lg-10">
<h1 class="text-center mb-4">
Integrated Human Practices
</h1>
<hr>
<section>
<h2 class="section-title text-center">Heading 2</h2>
<h4 class="subsection-title text-center">Heading 4</h4>
<p>Proteinopathies are a group of disorders associated with the misfolding, aggregation, and deposition of proteins, leading to loss of functionality and ultimately resulting in cell death. A lot of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease are examples of proteinopathies. Understanding the mechanisms of the proteinopathies is challenging due to the underlying complexity of protein folding, the rich interwebbing of multiple important cellular pathways, and the unique pathophysiology of each disease. Proteins interact with various other macromolecules in the cell such as - other proteins, lipids, and nucleic acids. These interactions usually affect and influence the stability, localization, and function of a protein in its native state. Understanding these networks is essential to deduce which pathways are involved and get affected in proteinopathies.
Proteinopathies also exhibit a broad abstract range of symptoms which seem to overlap with a range of other age related disorders. Disease progression, even amongst patients with the same diagnosis, seem to differ and vary a lot. This heterogeneity complicates the identification of common underlying mechanisms and hence effective therapeutic targets. Several animal models and cell cultures often fail to replicate the complexity and exactitude of human diseases accurately. While these models provide valuable insights and intuition, they may not capture the full spectrum of pathology seen in patients. Unfortunately, many proteinopathies show clinical symptoms only after extensive damage has already occurred, making early diagnosis potentially very challenging. The underlying pathology may already be well-established, hence leaving the clinician with limited therapeutic options.
</p>
</section>
<section>
<h2 class="section-title text-center">Heading 2</h2>
<h4 class="subsection-title text-center">Heading 4</h4>
<p>
In 2018, Aptamers were raised on several peptide segments of Tau, one of them being Thr-231; we then proceed to use those same aptamers as our beginner pool to start our process of SELEX. We expect evolving the affinity of our aptamers over randomly phosphorylated Tau-441 using GSK3β, having at least the 231 Threonine site phosphorylated. However, to reduce the scope of uncertainty, we decided to model the pathological Tau using 'phosphomimetics'. In this method, the phosphorylated substrate is substituted by a structurally similar acidic amino acid. By this, we can mimic the physical structure of the phosphorylated compound (which is what the aptamer binding mechanism depends on). However, we still reckon that the aptamers for the p231 Tau might not be completely compatible with our modifications, hence we also plan to run SELEX on them to generate a final pool of specific, affine aptamer for our investigations.
</p>
</section>
<div class="alert alert-warning mt-4">
<h4 class="alert-heading">DISCLAIMER</h4>
<hr>
<p>
We are not claiming to develop a 'cure' or 'therapeutic' for AD, we are just planning to explore the limits of Aptamer technology with the hopes that it can be one day modelled successfully for a therapeutic application. While research on cell lines and mouse models have shown that TPD can be a very promising potential treatment strategy, it is NOT established via human trials. Hence, the possible side effects of such a strategy are not well understood. We are only wishing to expand the global scientific knowledge.
</p>
</div>
<p class="mt-4">We hope to inspire future researchers to use our idea as a template for tackling other proteinopathies and also to expand and build on our core idea.</p>
<link href="{{ url_for('static', filename = 'blog.css') }}" rel="stylesheet">
<h1 class="text-center padding display-4"><b>IHP</b></h1>
<div class="d-flex flex-wrap row">
{% for blog in ihpbloglist: %}
<div class="card-mb-4 col-lg-3 col-md-6 col-sm-12">
<div class="card-body">
<h5 class="card-title">{{ ihpbloglist[blog]['title'] }}</h5>
<p class="card-text">{{ ihpbloglist[blog]['author'] }}</p>
<a class="btn btn-primary" href="{{ url_for('ihpblog', blog=blog) }}">Read</a>
</div>
</div>
{% endfor %}
<div style="height: 10rem;"></div>
</div>
{% endblock %}
{% extends "layout.html" %}
{% block title %}{{ blog.metadata.title }}{% endblock %}
{% block lead %}IHP post by {{ blog.metadata.author }}{% endblock %}
{% block page_content %}
<link href="{{ url_for('static', filename = 'blog.css') }}" rel="stylesheet">
<div class="container">
<h1 class="text-center display-4">{{ blog.metadata.title }}</h1>
<p class="text-muted text-center">By {{ blog.metadata.author }} | {{ blog.metadata.date }}</p>
<div class="blog-content">
{{ blog | safe }}
</div>
<a href="{{ url_for('pages', page='ihp') }}">Back</a>
<div style="height: 10rem;"></div>
</div>
{% endblock %}
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