MGM SUMMER UNDERGRADUATE RESEARCH ENGAGEMENT (MGM SURE)
The Department of Molecular Genetics and Microbiology is pleased to continue for the third summer a 10-week summer fellowship program for Duke undergraduates. The program runs from June 1, 2017 – August 5, 2017.
The goal of undergraduate research opportunity is to introduce motivated students to important questions in Genetics, Microbiology, Infectious Diseases, Virology, and RNA Biology through faculty-mentored research projects and practical lab experience. The program also includes monthly science and career development discussions with faculty and trainees (graduate students and postdocs) in MGM. The research experience culminates in MGM SURE fellows presenting their summer research project at the department’s annual retreat in early September.
Overall, the program aims to capture students who are interested in developing a research project in an MGM lab during their undergraduate years at Duke and completing their senior thesis based on this research. The program also aspires to prepare students to become scientific scholars immersed in sustained long-term pursuit of biomedical research.
Research in the Department of Molecular Genetics and Microbiology spans both model and pathogenic organisms and the full spectrum of genetics from unicellular to multicellular eukaryotic organisms. Many investigators are experts in both microbiology and genetics, including those utilizing yeasts as experimental microbial systems, and those probing the interactions of infectious agents with cellular or heterologous host model systems. Much of the history of modern molecular biology can be traced directly to genetic approaches with microbial and infectious systems, including the discoveries of DNA and RNA as the genetic material, the elucidation of the genetic code, and the development of recombinant DNA approaches based on bacterial restriction-modification systems and related enzymes. Existing areas of strength in the Department include: 1) microbiology (virology, mycology, bacteriology); 2) RNA biology and genomic expression analysis; 3) fungal genetics; 4) genetics of model systems and humans; 5) chromosome structure, function, replication, and repair, and 6) epigenetics.
Eligibility and Criteria
MGM SURE is open to Duke undergraduate students who have completed or are currently enrolled in at least one biological sciences course. With the exception of graduating seniors, all Duke undergraduates are eligible to apply. Prior research experience is not required, since a goal of the program is to immerse students in cutting-edge research labs where they can acquire skills in experimental practices, data analysis and interpretation, and effective science communication. Those undergraduates currently involved in research in MGM labs are also eligible to apply. Candidates not currently working in MGM labs are encouraged to contact faculty of interest prior to submitting an application to discuss the possibility of doing summer research in a particular lab.
We encourage women and individuals from underrepresented groups to apply. Students will be selected based on academic record, letters of recommendation, and descriptions of research interests and goals.
The research engagement will run from June 1, 2017 – August 5, 2017. Students should be present full-time for the entire summer program, and ought not be enrolled in courses during the research engagement period.
Number of Awards
In Summer 2017, MGM SURE will grant 4-6 awards to support summer research projects of ~10 weeks in duration. Each award includes a $4000 stipend (to help cover accommodation and living expenses for 10 weeks) and $1000 in project expenses to be paid to the host lab. Note that housing/accommodation is not provided or coordinated by the program.
Projects involving human subjects, either in-person or online, may need approval from the Duke Institutional Review Board. All MGM SURE fellows will be required to complete the necessary online safety training offered through the Duke Safety Office
2017 MGM Sure Students
Influenza is a virus with a segmented genome consisting of 8 RNA segments that collectively encode a total of 11 proteins. Each segment contains non-coding, conserved genomic ends, as well as internal segment-specific coding regions towards each end of the RNA strand. These segment-specific regions act as ‘packaging signals’ and evidence has shown that they influence the way influenza selectively incorporates each vRNA segment into viral progeny. The mechanism by which these packaging signals interact to accomplish selective packaging is not known – vRNA-vRNA or vRNP-vRNP interactions are hypothesized. In order to better understand the role of packaging signals in progeny genome packaging, we will take two approaches. The first involves the creation of viruses that possess 7 wild type segments – the HA and NA segments, however, will be cloned to be flanked with the other’s packaging signals. A virus will be grown that contains 7 wild type segments with a HA segment flanked by NA signals; another will be grown with 7 wild type segments with a NA segment flanked by HA packaging signals. One of these viruses has already been rescued by Alfred Harding, the graduate student I will be working with. I will need to purify and sequence it, after which we will compare the sequence of the packaging signals to wild type. The second approach involves mutagenesis in the packaging signals of HA and NA. We will use error-prone PCR to generate mutations within the packaging signals for HA and NA, allowing us to create a library of mutants. We will then transfect cells with viral constructs containing these mutant packaging signals and recover any virus that is produced for purification and sequencing. With this method, we will be able to compare mutants to wild type and can discover which aspects of the packaging signal sequence are conserved and which are subject to mutation. It is expected that this information will provide insight as to how the packaging signals interact.
Epstein-Barr virus latently infects B lymphocytes and drives them to proliferate through nine latency proteins, leading to Burkitt’s and several other B cell lymphomas. Of the nine latency proteins, four Epstein-Barr nuclear antigens (EBNAs) bind to and modulate the activity of transcription factor RBPJ, the downstream DNA binding component of the Notch signaling pathway. Because RBPJ-EBNA interactions are the primary way for Epstein-Barr virus to access DNA to induce cellular replication, the RBPJ-EBNA interactions are critical for promoting cellular proliferation. I aim to biochemically and structurally characterize these RBPJ-EBNA interactions to facilitate future rational structure-based development of small molecules that can disrupt these RBPJ-EBNA protein-protein interactions to treat Epstein-Barr virus associated malignancies.
Given the increasing use and reliance on cell phones, concerns about cell phone radiation having the potential to cause or increase the risk of cancer are rising. I am researching the effect of cell phone radiation on mutagenesis and looking at what repair pathways could be involved. I am also looking into mutagenesis caused by alcohol, as alcohol consumption is associated with increased levels of cancer. The main carcinogen from alcohol consumption is believed to be a bi-product of EtOH metabolism, acetaldehyde. Acetaldehyde can create interstrand cross-links and DNA base adducts. Previous research in human cells has shown that cross links may be repaired by NER (RAD14 in yeast). We also hypothesize that HR could be involved in repair as well. In both projects, we can monitor mutagenesis using CAN1 and LYS2 window sequencing, in addition to using fluctuation assays for the alcohol project.
I am a rising Junior at Duke University majoring in Biology with a minor in Chemistry. This summer, in Dr. Dong Yan’s lab, I will be exploring neurodevelopment using C. elegans as a model system. More specifically, I will be investigating how the protein MLS-2 is involved in a simple motor neural circuit, the RME circuit, in order to understand the molecular mechanisms underlying neural circuit formation. I will also be exploring glial cell development in C. elegans to further understand these important yet often overlooked components of the nervous system.
Cryptococcus neoformans is a human fungal pathogen that has been found to invade the central nervous system of humans especially those with weakened immune system such as HIV patients, ID transplant patients, diabetic and cancer patients, to mention but a few. Annually, it is responsible for over 600,000 deaths, mostly among HIV patients in Sub-Saharan Africa and Asia (Park et al., 2009). Our lab previously identified genes critical for survival in CSF through the development of an ex vivo CSF survival assay (Lee et al., 2010). How C. neoformans crosses the blood-brain barrier to cause disease remains a mystery. In this study, we will characterize genes enriched at the site infection via phenotypic assessments to assess how the pathogen overcomes the unique stresses i.e oxidative stress and temperature of 37oC, present in the human cerebrospinal fluid. Using 19 deletion strains from Madhani deletion library and 2 mutant strains I created, various virulence-associated factors such as Capsule and melanin production will be evaluated. Since these genes are highly expressed in two different clinical isolates from human CSF directly, I will also evaluate the specificity of each gene’s expression under in vitro and in vivo conditions to identify positive hits. In cases where the gene expression is specific to in vivo conditions, I will prepare a reporter strain that will allow me to visualize expression in vivo using the zebrafish model. Furthermore, deletion strains will assessed for their ability to cross the blood-brain barrier using the IV mouse model. The results of this study will characterize of genes of unknown function and further characterize the role(s) of described genes.
My research is based on determining the function of 2 genes within Saccharomyces cerevisiae with one being a putative epoxide hydrolase, utilizing colorimetric epoxide hydrolase and protein over expression assays.