Methylenetetrahydrofolate-reductase (MTHFR) is an enzyme involved in the synthesis of methionine, an essential amino acid. Due to MTHFR importance for cellular health, Jessica studies MTHFRs in yeast species Saccharomyces cerevisiae through analysis of paralogous genes MET12 and MET13. The Met12 and Met13 proteins are both MTHFR enzymes, however based upon biochemical results Met12 appears to be non-functional. Recently Jessica showed that Met12 has been non-functional for millions of years, since it also lacks function in yeast species Saccharomyces bayanus. Since yeast aggressively remove non-functional elements from their genomes, this result is strong and presumptive evidence that Met12 has an important, undetected function. Jessica’s experiments will describe why Met12 is nonfunctional, and will test the hypothesis that physical interactions between Met12 and Met13 are important for cooperative maintenance of methionine bioavailability.
Tuberculosis (TB) is an infectious disease that often attacks the lungs and can be spread through the air by coughing, sneezing, and other airborne means. Approximately 2 billion people are infected with TB and around 1.6 million people die of this disease every year. Navpreet will develop a point of care (POC) diagnostic device that will be able to quantify specific TB biomarker levels in serum using electrical impedance spectroscopy. His project tests the hypothesis that the limit of detection can be improved by creating a 3D gel sensor as opposed to the standard 2D sensor for electrochemical detection. The versatile, low cost POC platform technology for TB diagnosis and other antibody-based assays will address the existing diagnostic needs of patients and clinicians in underserved regions.
Metabolic engineering has the potential to provide environmentally friendly routes for the synthesis of a variety of molecules, including therapeutics and biofuels. One way to improve the flux of metabolic pathways is the use of synthetic protein scaffolds that colocalize enzymes in the engineered mevalonate biosynthesis pathway. Susan’s project tests the hypothesis that optimal scaffolds of certain architectures mimic substrate channeling and function by forming large, oligomeric complexes that bring scaffolds into close proximity. Adaptor molecules are synthesized that co-assemble scaffolds to designably control complex size. Mevalonate product titers will be measured using GCMS, and protein colocalization will be verified by fluorescence imaging. The successful engineering of this adaptor strategy can be applied to other pathways due to its modularity.
The bacterium Salmonella is a significant cause of food-borne disease. Its pathogenesis depends on the type III secretion systems (T3SSs) that were acquired by horizontal gene transfer; the invasion of Salmonella into the host cells requires appropriate expression of T3SSs. Recent research has identified small non-coding RNAs (sRNAs) as a class of regulators that fine tune gene expression required for bacterial physiology and pathogenesis. Elton will investigate the specific interaction between one of these newly discovered Salmonella sRNA and its predicted candidate targets; he will characterize the interaction between IsrM and its cognate targets, HilE and SopA, and identify the mechanisms of these interactions. The research work on the interaction between this sRNA and its targets will contribute towards a more complete understanding of the molecular coordination of Salmonella pathogenesis.
Transposable elements (TEs) are movable pieces of DNA that can have detrimental effects in the plant genome. When TEs are expressed, they can disrupt normal gene function. Small RNAs (siRNAs) direct DNA methylation, which signals other proteins to prevent TE expression. Previous studies show that methylation patterns in the endosperm affect silencing of TEs in the embryo, and propose that siRNAs from the central cell, a female supporting germ cell, mediate TE silencing in the egg cell. Denisse will test the idea that siRNAs move from the central cell to the egg cell and silence TE expression in the egg cell. To achieve this goal, she will generate transgenic plants that produce specific siRNA-like molecules in the central cell and will determine if they move to the egg cell.
Rapid land use transformation worldwide in recent years raises a demand for models that simulate the impacts of different land use policies on the local ecosystems and its services for human well-being. Mio will join a team in Brazil and devise a mathematical model that estimates the impacts of local land use choices on the carbon sequestration abilities of Atlantic Forest. She will integrate the devised model into Multiscale, Integrated Models of Ecosystem Services (MIMES), which collaboratively simulates the impacts of different land use policies on ecosystem services provided by the forest. This research will contribute to the development of effective land management policies that lead to sustainable conservation of Atlantic Forest. Furthermore, identifying the benefits, requirements and limitations of the modeling methods will provide valuable references for future studies.
Technologies based on superconducting quantum systems have contributed significantly to the development of high precision magnetic sensors and quantum bits. These experiments require ultra-low temperatures which are achieved by dilution refrigerators. In contrast to conventional dilution refrigerators, which generally require a continuous supply of liquid helium and complex circulation systems, the dilution refrigerator Yu-Dong aims to construct will not use liquid cryogens and mechanical pumps. This will be accomplished by integrating a 2-Kelvin pulse tube cryostat with a self-contained dilution unit prototype from Chase Cryogenics, to further lower the base temperature to 50 milli-Kelvin. This novel dilution refrigerator will be fully computer controlled to optimize cool-down and hold-time, serving as an easy to use, fast cycling system for experiments on superconducting quantum mechanical systems.
RNA interference (RNAi) is a rapidly expanding field of research that promises to yield a better understanding of how cells regulate their environments through RNAi mediated gene silencing pathways. Harnessing RNAis transformative properties may prove to be a powerful methodology for developing effective, cell-specific drugs, thus reducing harm and unwanted side effects. Alison’s project involves reconstituting the piRNA biogenesis machinery in vitro; specifically, elucidating the role of the protein, Squash. piRNAs are a recently discovered class of small regulatory RNAs that are thought to facilitate transposon silencing through RNAi, thereby protecting the genome from the deleterious effects of insertional mutagenesis, some of which have been implicated in cancer cell life cycles. Understanding these key mechanisms of gene regulation could radically transform the treatment of many genetically-linked diseases.
Jason’s research group has recently developed the nanocalorimeter, a membrane-based calorimeter which has ten times less addenda heat capacity than any known calorimeter, allowing for the first accurate measurements of nanogram sized samples. With this, Jason proposes to measure the specific heat of silicon nanowires in response to recent thermal transport studies. These studies have found that the thermal conductivity of silicon nanowires decreases with decreasing nanowire diameter. Such a characteristic means silicon nanowires have a big future in clean energy thermoelectric devices. But before we can properly exploit them in technology, their thermal dynamics must be better understood. Directly related to the phonon density of states, specific heat will help Jason explain the decrease in thermal conductivity by investigating phenomena such as phonon confinement and surface vibrational states.
Multidrug efflux pump, which sometimes pumps out almost all of the commonly used antibiotics, plays a major role in bacterial resistance. The design of better antibiotics which will overcome this mechanism will require knowledge of the kinetic behavior of this pumping process. Recently, Cheng participated in a study that determined the kinetic constants for one class of antibiotics, cephalosporins. In this project Cheng will be using other antibiotics as the potential competitor of the cephalosporin flux to develop a more complete understanding of kinetic behavior of the pump. The knowledge of kinetic constants for various antibiotics will allow design of more suitable compounds that will evade the multidrug efflux process and will be effective in the treatment of human infections in the 21st century.