Undergraduate Summer Research Internships
The Systems Biology community at Harvard invites interested undergraduates who will not have graduated by June 2014 to apply for research internships in the summer of 2014. Deadline for applications AND recommendation letters is February 21. Applicants can find the application forms here.
Starting on Monday June 9 the internship will last for ten weeks (until Aug 15). Interns will work on research projects in the
labs of the Bauer Fellows and Systems
Biology faculty whose work spans many fields of science, from biology
(including systems biology, biophysics, boinformatics and genomics)
to applied mathematics and computation. Interns will have the opportunity to learn a range of cutting-edge
genomics or bioinformatics techniques in the exciting and dynamic research environment at
the FAS Center for Systems Biology and the Department for Systems Biology at Harvard Medical School.
The internships will be offered to Harvard
students and students from other US universities. Underrepresented minority students and students from disadvantaged backgrounds are particularly encouraged to apply. We consider applications from rising sophomores, juniors and seniors. Unfortunately we cannot consider international students unless they are enrolled at US universities and have valid student or work visas.
Interns will receive a competitive stipend and Harvard housing (Harvard students can opt out if they have housing through PRISE). Harvard students are also encouraged to apply for PRISE and HCRP fellowships. In addition to the research program, the internship includes field trips to local research institutes, weekly seminars, lectures by distinguished faculty, and social and career events coordinated with other Harvard internship program.
In addition to completing the online form here, applicants will be asked to submit a resume, transcripts (inofficial transcripts ok), a research statement and an optional personal statement. Intern candidates can apply for up to 3 projects which are listed below. In your research statement please specify why you are particularly interested in the chosen projects. This description plays an important part in the selection process. You will also be asked to provide contact information for two referees who should know you from prior or current academic or research activities. They will be asked automatically to upload their recommendation letter AFTER you submitted your application material. Please make sure that they are willing to serve as a reference and share your application material with them well before the deadline so that they can prepare and submit a recommendation letter by the deadline of February 21. In fact, we advise applicants to upload their material at least a week before the deadline so that the referees have enough time to upload their letters.
Please have all required documents ready before you start filling out the forms since you will not be able to access an incomplete application at a later stage. For questions please contact Adriana Gallegosat agg "at" cgr.harvard.edu.
Internprojects in 2014
Project 1, Lauren O'Connell
1. Genetic basis of phenotypic diversity in posion dart frogs
Project 2, Nicolas Chevrier
2. Dissecting How Immunity Starts
Project 3, John Calarco
3. Exploring RNA diversity in the nervous system
Project 4, Rachel Dutton
4. What are microbes doing in my cheese?
Project 5, Andrew Murray
5. Reverse engineering genetic instability using evolution
Project 6, Pardis Sabeti
6. Massively Parallel Reporter Assay: Individual Loci Follow-up
7. Soft computing algorithm design and evaluation for population next-generation sequencing data
8. Functional followup on a site with excess synonymous constraint in Lassa virus
Project 9, Pamela Silver
9.What makes 'Conan the Bacterium' so tough?
Project 10, Sean Megason
10. Find small molecules that alter ear development
Project 1. Genetic basis of phenotypic diversity in poison dart frogs
Our group uses poison dart frogs to understand how the genome contributes to diversity within ecologically relevant traits. In the large family of dart frogs (family Dendrobatidae), there are many between and within species differences in toxicity, color morphology, and behavior. Our group focuses on two main research aims: (1) We use a comparative approach to learn more about the genetic and neural basis of parental care by comparing species where only the males care for offspring to other species where only females care for offspring. (2) We use molecular tools to better understand how the genome of a single species can produce such diversity in phenotypes, as many species have over thirty different color patterns advertising their toxicity to potential predators. Interns will have the opportunity to work with the frogs and learn molecular techniques at the lab bench, including RNA sequencing, immunohistochemistry and microscopy.
Project 2. Disecting how immunity starts
We study how immune responses arise in mammals using cellular and mouse models of infection and vaccination. Specifically, we are interested in dissecting the cellular circuits propagating information within the host during the initial hours and days upon immune activation. Understanding the rules governing how these circuits operate within and between organs will help designing new strategies for immune manipulation. We are looking for highly motivated students interested in helping develop new tools and approaches to characterize and manipulate the immune system. Depending on the candidate skills and interests, the project will involve mammalian cell culture, mouse work, molecular biology, and/or computational analyses (e.g., DNA or RNA sequencing, image processing, network analysis).
Project 3. Exploring RNA diversity in the nervous system
Our group uses C. elegans as a model system to investigate how cell-type specific regulation of gene expression is achieved, and to better understand the physiological consequences of given gene regulatory events in creating molecular and cellular diversity. We are particularly interested in understanding how a particular pre-mRNA processing step known as alternative splicing can influence the development and function of the nervous system. Using recently developed fluorescent reporters, we have identified a number of genes with mRNA transcripts that are differentially spliced in specific classes of neurons. We are now interested in identifying the factors responsible for this differential splicing regulation, and we also wish to determine how these splice variants contribute to the myriad of functions performed by the nervous system. Interested students would have the opportunity to learn and utilize classical and molecular genetic techniques, biochemical approaches, and microscopy to explore these questions. Experience in any of these areas will be helpful but not a prerequisite.
Project 4. Cheese as a model microbial ecosystem
In an effort to understand how microbes behave in complex environments, we are using cheese as a simplified model system. Our lab is characterizing the microbial communities found on a variety of cheeses, using deep sequencing, metagenomics, and microbial culturing. Summer interns would be involved in the study of the cheese microbiome using lab-based experimental communities, specifically with the goal of characterizing the functions and interactions of different species. Projects are also available to study the genetic diversity and evolution of cheese microbes through the analysis of sequencing data from the individual genomes of cheese microbes and the metagenomes of cheese communities. Students with interests and/or a background in microbiology or bioinformatics/programming are encouraged to apply.
Please visit our lab website for more information: https://sites.google.com/site/theduttonlab/home
Project 5. Reverse engineering genetic instability using evolution (with Miguel Coelho)
Two opposing forces influence how accurately cells transmit genetic information: the deleterious nature of most mutations and the accurate replication and segregation of chromosomes favors genetic stability, but strong selective pressures can favor genetic instability, mistakes in replication and segregation that can give cells growth advantages. During cancer progression genetic instability evolves because it speeds the accumulation of mutations that turn normal cells into cancerous ones. Theoretical analysis suggests there may be an optimal mutation rate for cancer evolution, with higher or lower rates slowing cancer progression.
In this summer project, we will create “cancer” yeast strains that are very genetically unstable, ask how fast they evolve, and ask how their level of genetic instability changes in different environments. We will inactivate both mechanisms that ensure the accuracy of DNA replication: the proof-reading activity of DNA polymerase, which checks that the enzyme has just inserted the correct base, and mismatch repair, whose enzymes scan the DNA after it has been replicated, looking for mistakes that the polymerase’s proof-reading has missed. This is an ambitious project designed to ask what limits rates of evolution and how easily cells can mutate to optimize their own mutation rates. The student will learn how to use experimental evolution to interrogate biology, and advance his lab skills (experimental design, data analysis, poster and oral presentation), while learning molecular biology, live cell microscopy and whole genome analysis.
Requirements: A motivated student with willingness to learn and participate in the interactive scientific atmosphere in our lab.
Project 6. Functional Characterization of Candidates for Natural Selection (with Ryan Tewhey)
While hundreds of genomic regions have been identified as having strong evidence of recent natural selection in humans, few underlying mutations and adaptive traits have been elucidated. Our lab has recently developed a computational method, the Composite of Multiple Signals, that allows for fine mapping of candidates, at 20-100x improvement in positional resolution, and have already begun to elucidate adaptive variants. For example, using a mouse knock-in model, human genetic association, and population genetic analysis, we showed that the adaptive mutation EDAR370A likely arose in Central Asia over thirty thousand years ago, and resulted in increased eccrine sweat gland numbers, thicker and straighter hair, and decreased mammary gland size. We are now developing a high-throughput experimental framework to rapidly pinpoint and validate biologically important human mutations under selection. We have already identified several top candidates and will be moving to computationally and functionally characterizing them towards understanding adaptive traits in humans.
Project 7. Detection of Microbes Causing Febrile Illness (with Xiao Yang, Kristian Andersen)
Many infectious pathogens produce non-specific symptoms like fever, headache, and nausea, making them difficult to diagnose clinically. It is estimated that 30% to 90% of all hospitalized patients with acute fever in tropical Sub-Saharan Africa are diagnosed as malaria and treated with antimalarial drugs, while only 7% to 45% of them have laboratory-confirmed malaria, and only a fraction of these actually have malaria-induced fever. Microbial metagenomics has the potential to transform our understanding of disease-associated pathogens around the world. It is a powerful tool for pathogen discovery because it does not require culturing, cloning or a priori knowledge of the microbes present. Further breakthroughs in computational analysis are still needed. We aim to design and validate a soft computing algorithm for population next-generation sequencing data toward fully enabling characterization of fever-causing viruses from around the world.
Project 8. Functional characterization of adaptive variation in Lassa virus (with Rachel Sealfon, Kristian Andersen)
Lassa virus (LASV) is among a small group of hemorrhagic fever viruses, designated biosafety level 4 (BL-4) agents for their high fatality rate and potential for aerosol transmission. Lassa fever (LF) hospitalizes tens of thousands and causes several thousand deaths each year, with case-fatality rates in excess of 50%. Given LF’s prevalence and impact, surprisingly little is known about it; like other BL-4 agents, its lethality at once poses a global risk and impedes investigation.
Our lab has developed partnerships with Kenema Government Hospital, Sierra Leone and Irrua Specialist Teaching Hospital, Nigeria. Together with international partners, we implemented diagnostics, infrastructure, training, and safety measures to ensure standard-of-care medical support and high quality and safe sample collection from LF patients. We have now sequenced over 100 LASV strains (the largest catalog of BL-4 pathogens to our knowledge) and have investigated LASV’s origins, evolution, and pathogenicity. We have identified a number of intriguing adaptive variants in these loci, which we will be functionally validated and characterizing using safe model systems.
Project 9. What makes 'Conan the Bacterium' so tough? (with Roger Chang)
Deinococcus radiodurans has an extraordinary ability to resist and recover from some of the harshest conditions, including exposure to ionizing radiation. This ability is linked to unusual DNA repair mechanisms and protection of its proteome from damage by oxidative radicals; however, the full mechanism and key targets of protein protection remain incompletely understood. Uncovering this basis for resistance may have important implications in co-treatment for radiation therapy and investigating the role of protein oxidation in aging processes. In this interdisciplinary project, we will develop bioinformatics methods to predict vulnerability of protein structures to oxidative damage and reconstruct a genome-scale metabolic network model in which to simulate metabolic sensitivity and recovery from irradiation. Predicted key mechanistic players and targets will be studied through experimental genetic knock-outs and assays for protein oxidation. We will also develop an experimental method to decouple the effects of proteomic protection and chromosomal repair in response to irradiation using fluorescence-activated cell sorting with labeled chromosomes in living cells, a method that will also be useful in quantifying the dependence of DNA repair mechanisms on multiple genomic copies. We are looking for highly motivated students interested in interdisciplinary research. Depending on candidate skills and interests, the student would have the opportunity to learn protein structural analysis, high-scale network modeling, bacterial culturing, genetic transformation, biochemical assays, flow cytometry and fluorescence-activated cell sorting. Experience in any of these areas would be helpful but is not required.
Project 10. Find small molecules that alter ear development
Abnormalities in our senses of hearing and balance are incapacitating in the extreme, and, when more subtle, cause psychological distress. The homeostasis of the adult ear ensures these senses remain intact. The mechanisms that drive ear development and growth are related to the mechanisms that maintain a healthy adult organ. Additionally, congenital defects in ear development can cause hearing and balance syndromes. To identify tools for studying ear development as well as potential therapeutics we propose a search for small molecules that alter ear growth and morphogenesis. These studies will be performed in the zebrafish whose small size, rapid development, and optical clarity allow high throughput identification of drugs that alter the ear’s development. Additionally, we will take advantage of zebrafish genetics with ear mutants to identify molecules that enhance or suppress mutant phenotypes related to ear health.