BIOTECHNOLOGY TRAINING PROGRAM
Irene M. Brockman - Prather Research Group
Research Project: Controlled protein degradation for development of metabolite valves
A variety of gene knockout and genetic control strategies have been used to redirect flux into heterologous biosynthetic pathways in microorganisms. However, for many pathways, the ideal targets for control are part of the central carbon metabolism of the host, and downregulation of these enzymes may result in poor growth on the desired substrate. My research is focused on strategies for dynamically modulating the abundance of key enzymes within the host cell, allowing for switching between growth and production modes as flux is directed away from central metabolism. I am especially interested in targeted protein degradation, since it allows enzymes to be rapidly depleted even under conditions of slow growth.
Robert Citorik - Lu Lab
I am working in Dr. Timothy Lu's laboratory as part of the MIT Synthetic Biology Center. After getting a B.S. in microbiology and spending a few years researching bacterial pathogens at MGH, I found myself excited to enter the rapidly growing field of synthetic biology and apply it to infectious diseases. One of the largest problems we face today is the emergence and expansion of highly resistant microbes that are capable of causing disease while confounding many or all available antibiotic treatments. Both the nature and importance of this problem warrant exploration of alternative treatment strategies. My current research involves working with new tools in genomic editing to specifically target resistant populations for modification or elimination.
Christi Dionne Cook - Griffith Lab
Research Project: I am interested in characterizing rare cell populations in the peritoneal cavity of endometriosis patients. My research involves developing better quantitative models to characterize the dynamics of endometrial cell proliferation and invasion, using a combination of biomaterials scaffolds, high throughput imaging, and computational analysis.
Adam Freedman - Thompson Laboratory
Research Project: I am interested in biochemical processes that utilize microbial conversions of byproduct wastes or greenhouse gases to produce clean fuels, useful biodegradable materials and aid in effective carbon management. My interests lie most directly at the point where microbiology, genetic engineering and sustainable energy converge, as I will explore the potential for introducing biofuel-producing genes into various bacterial species.
Furthermore, I am interested in how microbes affect the geochemistry of deep subsurface environments after injection of high-pressure CO2. To that end, I am researching the extent to which microbes catalyze biomineralization under high-pressure CO2 conditions, a process that has the potential to reduce CO2 migration/leakage and improve the sealing capacity of reservoirs targeted for geologic carbon sequestration.
Matt Glassman - The Olsen Laboratory
Research Project: Hydrogels are an exciting platform technology for biomedical solutions in many high impact areas, from managing chronic ailments such as rheumatoid arthritis and osteoporosis, to treating acute conditions such as hemorrhaging and cancer. Precisely engineered injectable hydrogels could enable minimally-invasive surgical implantation for improved control in the delivery molecular and/or cellular cargo within bioactive, degradable scaffolds. We are developing new methods for engineering shear thinning hydrogels that can be thermoresponsively strengthened post-injection to yield tough implants that can bear significant physiological loads. By utilizing artificially-engineered proteins conjugated to designer polymers, we are synthesizing biomaterials that are finely tuned for protecting and communicating with encapsulated cells, integrating with host tissues at the target site, and executing predefined programs for nanostructure formation and controlled release. Fundamental studies on the structure and mechanics of double physical network hydrogels (which consist of two independent, reversibly-associating networks) will enable the development of enhanced materials to meet clinical demands.
Nicole Kavanaugh - Ribbeck Laboratory
Research Project: My primary research focus is understanding the interactions between pathogenic microbes and mucus. Mucus is an important biological barrier inside the human body that functions to keep harmful microbes from causing infections. I hope to understand the mechanisms by which mucus provides this protection in order to develop new anti-infection strategies.
Jennifer E. Kay - Engelward Laboratory
Research Project: My research is on DNA damage and repair with a focus on homologous recombination. We are especially interested in the role of the repair gene Brca2 in HR. In vitro, I induce double strand breaks in cells of various genotypes, then measure their repair capacity. In vivo, I have investigate the role of gut infections on DNA damage, inflammation and cancer in other organs.
Alexandria D. Liang - Lippard Research Group
Research Project: Ali works on protein-protein dynamics, electron transfer and proton transfer within the multicomponent protein toluene/o-xylene monooxygenase
Sarah Schrier - Lauffenburger Research Group
Research Project: Application of Modeling Techniques to Study Intercellular Signaling
Immune cells communicate to mount a response, often through the secretion of various cytokines or chemokines. Responses can be dynamic and involve the cooperation of many cell types. My project aims to further develop tools used to study intracellular signaling cascades to understand cell-cell communication, including both intracellular signals and their extracellular responses, with a particular focus on immunology and inflammation.
Rathi Srinivas - Doyle Group
Research Project: Encoded Hydrogel Microparticles for High Throughput and Multiplexed Biomolecule Detection
Robust biomolecule detection platforms are crucial in order to characterize disease states and advabce medical diagnostic tools. My work is focused on developing a novel microfluidic hydrogel-based system to understand protein and nucleic acid profiles in biologically complex media such as cell cultures and blood serum. Compared to a solid substrate, the three-dimensional and flexible scaffold of a hydrogel is more favorable for biological interactions and often offers higher sensitivity. Meanwhile, microfluidic synthesis and analysis techniques allow for rapid, high-throughput, and multiplexed quantification.
Mark M. Stevens - Manalis Laboratory
Research Project: Utilizing high precision mass sensing to directly measure cell response to nutrient depletion and cellular nutrient requirements
Despite exciting research targeting therapies to the metabolic changes seen in cancer cells, understanding metabolism well enough to take advantage of these differences remains a major challenge in cancer research. Still little is known about why these changes take place, what the basic metabolic requirements necessary for growth are, or how cells respond to changes in their metabolic microenvironment. In an effort to gain new insight into these questions, I am applying the femptogram-precision suspended microchannel mass sensor (SMR) to monitor cell growth and metabolism from the perspective of cell mass. With high temporal resolution, I am able to observe cell growth response to changes in its metabolic environment in real-time, and hope to elucidate some of the underlying mechanisms driving these response phenotypes.
Austin L. Travis - Imperiali Group
Research Project: Gram-negative bacteria have historically proven to be a challenging target for antibiotic development due to phentotypic difficulties as well as the continuing struggle with antibiotic resistance. A new paradigm of targeting virulence factors such as protein glycosylation rather than survival functions could present a key new indication for the discovery of novel antimicrobial agents. Additionally such a chemical tool would prove to be invaluable for studying the host-pathogen interaction in real time. A fragment-based drug discovery approach relying on chemical synthesis, x-ray crystallography, and several biological activity assays is being undertaken in order to develop a small molecule inhibitor of N-linked protein glycosylation.
Thomas Wasylenko - Stephanopoulos Laboratory
Research Project: Using 13C-Metabolic Flux Analysis and Metabolomics to Study Xylose Metabolism in Yeast and Microbial Fuel Cells
Microbes could play a key role in satisying the world's growing energy needs. We are using 13C-MFA and metabolomics to study the metabolism of the yeast S. cerevisiae growing on xylose and the metabolism of S. oneidensis in a Microbial Fuel Cell.
The cost-effective conversion of lignocellulosic biomass to biofuels will require a microbe that can convert the pentose sugar xylose to liquid fuel molecules. The yeast S. cerevisiae is a promising biocatalyst for biofuel applications, and although it does not natively consume xylose, xylose-consuming strains have been engineered. We are studying such a strain of S. cerevisiae growing on xylose to see how the metabolism changes when the strain is grown on this carbon source.
Microbial Fuel Cells
There are some microbes that are capable of using an electrode as a terminal electron acceptor, meaning these microbes can pass electrons from their carbon source to the electrode and produce an electrical current. Such a system, in which a microbe is used to generate electrical power through the oxidation of a carbon source, is called a Microbial Fuel Cell (MFC). We are studying a model MFC system with Shewanella oneidensis growing on lactate to see how metabolism changes when the electrode is used as the terminal electron acceptor.
Boyang Zhao - Lauffenburger Research Group and The Hemann Lab
Research Project: Recent high-resolution sequencing studies have revealed substantial intra-tumor heterogeneity in patients. This poses considerable challenges on the development of treatment strategies to eradicate all tumor subclones. Using an integrated approach of computational modeling and experimentation in the Eµ-myc lymphoma mouse model, we aim to investigate in vitro and in vivo how cancer therapies influence the clonal architecture and to develop therapeutic strategies for minimizing drug resistance.
Eric Zhu - Wittrup Laboratory
Research Project: Developing immunotherapies against tumors and elucidating mechanisms of the resulting immune response
Antibodies targeting tumor antigens and cytokine therapies have shown great clinical efficacy in treating tumors, but the underlying immunological mechanisms for their anti-tumor action remain unclear. Recent evidence suggests that combinations of these therapies can generate a potent host response against tumor challenge that requires both the innate and adaptive immune systems. I hope to elucidate the temporal mechanisms involved in this anti-tumor response and through this understanding develop additional agents to create more effective and long-lived treatments against tumors.