About This Project
The Michigan Synthetic Biology Team is developing a novel diagnostic device that will enable the detection of protein biomakers on a simple paper test strip. Our device will consist of a synthetic gene network freeze-dried on paper that uses the target specificity of aptamers and proximity-dependent ligation to detect protein biomarkers. This will create a convenient and affordable diagnostic method that can be used by medical professionals.
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What is the context of this research?
In recent publications, scientists demonstrated that transcription and translation can occur on pieces of paper . Using synthetic DNA circuits that were freeze dried on paper, researchers created genetic "switches" that emit certain signals. In the default off stage, no signal is exhibited. When the switch is turned on by a specific RNA trigger, the switch produces a protein output. These paper-based switches can be stored at room temperature for up to a year with no significant loss of function and can be produced for less than $1 USD/paper. Inspired by these advances, our project aims to put this technology to work. By developing a paper-based system to detect a particular target protein, we can potentially adapt this technology to diagnose a particular disease.
What is the significance of this project?
Tuberculosis (TB) is one of the leading causes of death worldwide according the World Health Organization , despite the fact that it is curable and treatments are often completely paid for by the government. Even so, 1.4 million died from TB in 2014 . Access to treatment isn't the problem. The problem is patients with TB are not being diagnosed until it is too late, since current methods are either cheap but only 50% sensitive, or are accurate but, prohibitively expensive or require access to advanced medical facilities. Our device would provide an inexpensive and reliable tool for diagnosis that could prevent this suffering. Also, our system could theoretically be adapted to detect any particular target, allowing expansion to detect other diseases.
What are the goals of the project?
Transcription and translation have been shown to occur on paper and freeze dried gene circuits are reconstituted with water [4}. While this is an exciting development, it is much more practical to detect diseases via proteins specific to the disease, rather than RNA or DNA. Our project uses a DNA aptamer to sense the protein, and then trigger proximity-dependent ligation, all on a cheaply produced paper test strip. We plan to harness this system to selectively produce an output visible to the naked eye upon addition of a liquid sample containing protein secreted by the pathogen. The same setup can be applied to any protein, thus making a detection system that will work for a multitude of diseases.
As an entirely student-run lab group, we count on your support to acquire the materials necessary to run experiments and make progress on our project. We rely entirely on donations and contributions form sources such as University of Michigan Academic Departments, generous corporations, and fundraising opportunities like this. Your contribution will directly fund the supplies we need to continue the research and development process and make this paper-based diagnostic tool a reality.
Due to the costly nature of the molecular biology supplies we need, the scope and range of our experiments are severely constrained by our available funds. Our current system lacks an effect amplification system when detecting target molecules, thus limiting the device's detection sensitivity. With additional amplification enzymes and isothermal PCR systems we will be able explore various systems to address this problem.
Meet the Team
The Michigan Synthetic Biology Team is a student led research club at the University of Michigan. MSBT annually enters the iGEM synthetic biology competition, an international conference/competition where hundreds of teams conduct independent synthetic biology research and share their findings. What’s more, as a student run organization from the ground up MSBT provides leadership opportunities that can’t be found in lab-based classes or by working in university research labs.
Alex Hadd is in his third year of study for a Chemical Engineering BSE with a minor in computer science and a concentration in the life sciences. He conducted developmental biology and biophysics research under Dr. Qiong Yang from September 2015 to May 2017. He is currently performing research in natural products chemistry and structural biology under Dr. David Sherman, investigating the structure and biocatalysis of polyketide synthase mega-enzymes via molecular cloning, protein engineering, and cryo-electron microscopy.
Irina Kopyeva is a rising sophomore studying Chemical Engineering with a life science concentration at the University of Michigan. For the past few summers she has worked in a colorectal cancer lab at the Cleveland Clinic, and also at the Weizmann Institute in Rehovot, Israel. Currently, along with MSBT, she is working in the Lahann Lab at UM with biomimetic polymers.
An advanced fellow in the Barger Leadership Institute, and studying Cellular & Molecular biology and Biomedical Engineering, Rachel Sun hopes to continue to work on pharmaceutical development after graduation. She has worked on possible applications of nanoemulsions as a vaccine adjuvant, and has developed a reporter system to study antisense oligonucleotide-based medications effects on Cystic Fibrosis.
Alex Girgis, a rising junior from Grand Rapids, is majoring in Biomedical Engineering with a biochemical concentration. Ultimately he will pursue a career in medicine. He currently conducts research in the Department of Surgery studying Pancreatic Cancer Immunotherapy under Timothy Frankel.
Aaron Renberg is an enthusiastic rising senior. He has previous research experience interning at the National Institutes of Health in Bethesda, MD and at Children’s National Medical Center’s genetic medicine department in Washington, D.C. In addition to MSBT, he is currently working on his honors thesis as an Honors Summer Fellow in the Soleimanpour lab at the Brehm Center for Diabetes Research at U of M. When a micropipet isn’t in his hand, it's usually replaced by a hockey stick or a fencing foil.
Nick Emery is a student at the University of Michigan studying Cell and Molecular Biology and Biomedical Engineering. Working towards cheaper, easier detection of protein biomarkers to improve disease diagnostics in developing countries and resource scarce settings. Also working in the lab of Dr. Allen Liu in the Department of Biomedical Engineering at University of Michigan.
Siddharth Madapoosi is a rising sophomore studying Microbiology at the University of Michigan. He has previous research experience studying deep vein thrombosis as well as obesity and metabolomics using murine models and hopes to pursue a career in epidemiology. Along with MSBT, he currently works under Dr. Vernon Carruthers of the UM Department of Microbiology and Immunology studying microbial pathogenesis.
Akira Nishii is a sophomore studying chemical engineering and biochemistry at the University of Michigan. He strives to become a physician-scientist (MD/PhD) in the "near" future. Along with MSBT, he plans to conduct research on cancer immunotherapy of brain tumors (glioma) under Dr. Maria Castro and Dr. Pedro Lowenstein of the Department of Neurosurgery.
Zach Bernstein is a rising sophomore studying Neuroscience in the Honors Program at the University of Michigan. Zach has had a variety of different work and academic experiences in business and sciences. He intends on minoring in The Ross School of Business and enjoys playing basketball and hiking.
Vijay Vobbilisetty is a third year Biomedical Engineering student at the University of Michigan. He is currently researching the genetic factors behind the development of aortic aneurysms and developing preventative therapies in the Department of Cardiac Surgery. Vijay has many varying interests, from discussing international policy on human rights as an ardent Model UN competitor to optimizing infrastructure at local nonprofit clinics.
Daniela Lewin is a junior in the Molecular Biology and Biomedical Engineering joint program at the University of Michigan. She is currently researching chemokines and receptors involved in breast cancer metastasis. Her other interests include dance, books and Latin American studies.
Cristina Castillo is a recent graduate from the University of Michigan in Cell and Molecular Biology. She has been part of MSBT for three years now and is currently an advisor for the team. She is also a research assistant in a physiology lab on campus. She studies the effects of hypoxia in cancer. She plan to continue my career as a scientist doing an MD/PhD program.
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Aptamers are strands of RNA or DNA that bind to proteins and small molecules with high specificity .
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