<p>Inflammatory Bowel Disease (IBD) is an indeterminate colitis and autoimmune inflammatory bowel disease that involves the ileum, rectum, and colon. Due to its unknown pathogenesis, it is difficult to cure and prone to relapse, which is then referred to as the “green cancer”. As the incidence of IBD is increasing globally, the poor therapeutic experience, which the patients are required to receive long-term hormone injection and biologic combination therapy, is determined to seek a breakthrough. Our team stands to develop a more favorable treatment experience. Relevant studies have shown that lactic acid has an inhibitory effect on abnormally activated dendritic cells and cytotoxic T-cells in autoimmune diseases, and thus is expected to improve the symptoms of IBD patients. Based on the research, we designed a yeast engineered bacterium. We introduced a muscone detecting switch in the engineered yeast and activated the downstream pathway to express lactate dehydrogenase to produce lactic acid. Ultimately, the engineered bacteria will colonize the small intestine, enabling the patient to treat IBD by inhaling muscone gas in vitro therefore induces the yeast to synthesize a low amount of stabilized lactic acid in vivo. Aroma therapy has the potential to be a new trend in long-term treatment for IBD as it can reduce the discomfort of treatment and improve the long-term treatment experience. </p>
<p>During our brainstorming process, we realized the mighty potency of synthetic biology in medical treatments, especially in the therapy development of inflammatory bowel disease (IBD), one of the hardest-to-cure conditions in the world. Thanks to the well-understood genetics and its efficient heterologous protein expression capacity, Saccharomyces cerevisiae appears to be a promising chassis organism for developing biological therapies for IBD. Additionally, various synthetic biology components enable us to design multiple control systems, achieving precise and comprehensive control over the treatment. Viewing IBD treatments from a brand-new aspect, we found that biological therapy obtains tremendous advantages not found in traditional chemical drugs. As a result, we have chosen IBD therapy as our project focus of this year.</p>
<p>Comprising of Ulcerative Colitis (UC) and Crohn's Disease (CD), IBD is a chronic, incurable disease affecting people of all ages worldwide. According to the Global Burden of Disease (GBD), there was a notable increase of 175,904 individuals diagnosed with IBD from 1990 to 2021. Over 1 million residents in the USA and 2.5 million in Europe are estimated to have IBD, with substantial costs for health care. IBD patients normally suffer from abdominal pain and diarrhea, combined with intermittent fever and various extraintestinal symptoms such as arthritis. Besides, IBD is well-known for its complex and unclear pathogenesis, which also explains why no common and satisfying therapy exists.</p>
<p>In our research effort, we discovered that abnormal immune response triggered by the intestinal flora is strongly related to the disease. Meanwhile, recent studies have revealed that lactate possesses the capacity to limit CNS autoimmunity response, thus relieving the inflammation in the intestine. As for the method of administration, to avoid the possible side-effects cost by oral administration, we take the advantage of recently-discovered muscone receptor, hoping that inhalational administration can balance both efficacy and comfortability.</p>
<p>IBD is now one of the most common intestinal diseases in China. Because of the relatively low public awareness of IBD and lack of rigorous standard for diagnosing IBD, many patients are misdiagnosed in the early stage of the disease, wasting valuable treatment time. Thus, we also put in effort to raise the public awareness and educate the public about IBD and intestinal health through various means.</p>
<p>Tsinghua University is a public university in Haidian, Beijing. It is affiliated with and funded by the Ministry of Education of China. The university is part of Project 211, Project 985, and the Double First-Class Construction. It is also a member of the C9 League. Tsinghua University's campus is situated in northwest Beijing, on the site of the former imperial gardens of the Qing dynasty. Currently, the university has 21 schools and 59 departments, with faculties in science, engineering, humanities, law, medicine, history, philosophy, economics, management, education and art.</p>
<p>Notable alumni who have held senior positions in Chinese politics include current general secretary and president of China, Xi Jinping, former general secretary and president of China Hu Jintao, former chairman of the National People's Congress Wu Bangguo, former premier Zhu Rongji, and the former first vice premier Huang Ju. This also includes politicians like Wu Guanzheng, former governor of the People's Bank of China Zhou Xiaochuan, former minister of finance Lou Jiwei, general Sun Li-jen, Liang Qichao, and more. Since 2016, Tsinghua graduates who have political prominence are disproportionately greater in number than graduates of other famous universities.</p>
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<p>Tsinghua University engages in extensive research and offers 51 bachelor's degree programs, 139 master's degree programs, and 107 doctoral programs through 20 colleges and 57 departments covering a broad range of subjects, including science, engineering, arts and literature, social sciences, law, medicine. Along with its membership in the C9 League, Tsinghua University affiliations include the Association of Pacific Rim Universities, a group of 50 leading Asian and American universities, Washington University in St. Louis's McDonnell International Scholars Academy, a group of 35 premier global universities, and the Association of East Asian Research Universities, a 17-member research collaboration network of top regional institutions. Tsinghua is an associate member of the Consortium Linking Universities of Science and Technology for Education and Research (CLUSTER). Tsinghua is a member of a Low Carbon Energy University Alliance (LCEUA), together with the University of Cambridge and the Massachusetts Institute of Technology (MIT).</pp>
<p>School of Life Sciences was first established in 1926 under the name Department of Biology. Botanist Qian Chongshu took up the first dean.During the nationwide reorganization of universities in the early 1950s, the Department of Biology was merged into other universities, namely Peking University etc., resulting in a vacancy in the field of biological research in Tsinghua for almost 30 years.In June 1984, decisions were made about the reestablishment of the Department of Biology, and the department officially reopened in September. During the reestablishment the Department of Biology of Peking University, the Institute of Biophysics of Chinese Academy of Sciences, and many other institutes as well as biologists provided valuable support and help. The department changed its name to the current name in September 2009. As of 2013, structural biologist and foreign associate of National Academy of Sciences of United States Dr. Wang Hongwei (王宏伟) is the current dean of School of Life Sciences. The school currently has 129 professors and employees, around 600 undergraduates (including the candidates of Tsinghua University – Peking Union Medical College joint MD program).</p>
<p>In recognition of the limitations of current IBD therapy, we embarked on a journey to harness the power of synthetic biology in developing a biological therapy, which we named “MusCure” as the abbreviation of “Muscone to Cure”. Our primary objective was to engineer yeast capable of specifically colonizing at the inflammatory sites of the intestine and delivering lactate in response to the signals of muscone.</p>
<p>Based on the published paper and our patient interviews, oral administration has many drawbacks. For instance, parts of IBD patients have difficulty in swallowing the pills, and given the vulnerable intestine of the patients, oral administration can cause further nausea or vomiting. To address the shortcomings of oral administration, MusCure offers an “APE” solution: “Affordable, Potential and Efficiency IBD treatment”. The following sections will elucidate how our design accomplishes these goals.</p>
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<p>Admission to Tsinghua for both undergraduate and graduate schools is extremely competitive. Undergraduate admissions for domestic students is decided through the gaokao, the Chinese national college entrance exam, which allows students to list Tsinghua University among their preferred college choices. While selectivity varies by province, the sheer number of high school students applying for college each year has resulted in overall acceptance rates far lower than 0.1% of all test takers. Admission to Tsinghua's graduate schools is also very competitive. Only about 16% of MBA applicants are admitted each year.</p>
<p>Department of Mathematical Sciences
The Department of Mathematical Sciences (DMS) was established in 1927.
In 1952, Tsinghua DMS was merged with the Peking University Department of Mathematical Sciences. Then in 1979 it was renamed "Department of Applied Mathematics", and renamed again in 1999 to its current title.
Tsinghua DMS has three institutes at present, the institute of Pure Mathematics which has 27 faculty members, the Institute of Applied Mathematics and Probability and Statistics which has 27 faculty members, and the Institute of Computational Mathematics and Operations Research which has 20 faculty members. There are currently about 400 undergraduate students and 200 graduate students.</p>
<h3>Current treatments</h3>
<p>Current treatments of IBD include surgical interventions, pharmacological therapies and nutritional therapies. However, these conventional IBD treatment methods still exhibit several limitations.</p>
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<p>Tsinghua University is consistently ranked among the top universities in the Asia-Pacific according to major international university rankings. Tsinghua University ranked No. 1 in China, the whole of Asia-Oceania region and emerging countries according to the Times Higher Education, with its industry income, research, and teaching performance indicator placed at 1st, 4th and 9th respectively in the world. Internationally, Tsinghua was regarded as the most reputable Chinese university by the Times Higher Education World Reputation Rankings where, it has ranked 8th globally and 1st in the Asia-Pacific.</p>
<p>The Engineering Research Center for Navigation Technology is a relatively young institute in the Department of Precision Instrument which was established in 2000, with the intention to "[pursue] excellence in the research and development in the field of high-accuracy inertial instruments and navigation technology, as well as in MEMS inertial sensor fields, and to provide advanced training for future scientists and engineers in the field of inertial technology." Its research interests cover high-accuracy inertial instruments and navigation technology, MEMS inertial sensors and systems, and precise electro-mechanical control systems and their application. As of 2012, the area of the center is 2900 square meters, including approximately 550 square meters of clean rooms. Equipment and instruments in this center are worth over 50 million RMB (US$7.56 million).</p>
<h4>Surgical Interventions</h4>
<p>Surgical interventions play an important role in the treatment of IBD, especially for patients who do not respond to medical therapy or who have complications. Surgical interventions are very effective, but because of the widespread use of ostomy techniques, they can have a significant negative impact on the patient's daily life as well as the injury.</p>
<h4>Pharmacological Therapies</h4>
<p>Pharmacological therapy is the core of IBD treatment, mainly including the following categories: aminosalicylic acid, glucocorticoids, immunosuppressants, biologics, antibiotics, probiotics, anticholinergics, etc. These drugs are usually immunosuppressive and increase the risk of infection with long-term use; Special targeted drugs have the disadvantage of being expensive.</p>
<h4>Nutritional Therapies</h4>
<p>Nutritional therapy plays an important role in the remission and prognosis of IBD. However, at present, nutritional therapy is faced with problems such as slow effect, long course of treatment, and insufficient targeting, which will affect the quality of life of patients.</p>
