Undergraduate Summer Research Internships

2011 Poster Session 2010

The Systems Biology community at Harvard invites interested undergraduates who will not have graduated by June 2012 to apply for research internships in the summer of 2012. The application deadline is February 20, 2012 (but please see below why we advise applicants to submit their material at least a week earlier: we need to receive ALL material, including the recommendation letters, by the Feb 20 deadline).

Starting on Monday June 4 the internship will last for ten weeks (until Aug 10). 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.

Applicants can find the application forms here. In addition to completing the online form, 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 a recommendation letter before February 20. 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 Bodo Stern at bstern "at" cgr.harvard.edu.

Intern Experiences in past years

Internprojects in 2012

Project 1, Peter Turnbaugh

1.Getting to know our trillions of microbial partners

Project 2, Michael Desai

2. Adaptation in Microbial Populations

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 5-6, Andrew Murray

5. Directing the evolution of plasmid 'species' in Escherichia coli

6. Investigating the fitness effects of division of labor

Project 7, David Nelson/Andrew Murray

7. Measuring competitive fitness on a surface

Project 8, Galit Lahav

8. Dynamics and function of p53 in embryonic stem cells

Project 9, Jeremy Gunawardena

9. Information processing in mammalian signal transduction networks

Project 10, Dan Needleman

10. Evolutionary Biology of Cell Division

Project 11, Roy Kishony

11. The synthetic biology of synonymous codon usage

Project 12-13, Michael Springer

12. Evolution of signaling pathways in yeast

13. Yeast as a model organism for mitochondrial disorders

Project 14, Philippe Cluzel

14. Stress in Bacterial Lineages

Peter Turnbaugh

Project 1. Getting to know our trillions of microbial partners

We never dine alone. Human beings are super-organisms composed of our own human cells and trillions of microorganisms, most of which are found in our gut. These microbial co-conspirators play important roles in health and disease. In particular, they aid in the digestion of our diet, and may influence the bioavailability, toxicity, and metabolism of orally administered drugs. We are looking for intrepid microbial explorers, who would like to use advanced 'metagenomic' methods, such as DNA extraction, PCR amplification, and next-gen sequencing to characterize these microbes with the goal of understanding and manipulating key factors that shape this complex community. We are also looking for students who want to tackle some of biology's largest computational problems. We generate and analyze hundreds of millions of microbial DNA sequences, looking for patterns that might help us learn about how microbes influence human health and disease. If you've got ideas for how to mine these data, we can provide the supercomputer time to test your code. Students with interests in machine learning, databases, or quantitative modeling are especially encouraged to apply.

See turnbaugh.openwetware.org for more info.

Michael Desai

Project 2. Adaptation in Microbial Populations

The basic laws of evolution are simple: mutations generate variation, while genetic drift, recombination, and selection change the frequencies of the variants. Yet even in very simple circumstances, it is often surprisingly difficult to predict how these forces interact to determine how a microbial population will evolve. We combine theoretical population genetics and experimental evolution to study how genetic variation is created and maintained in these microbial populations, and to infer the evolutionary history of populations from sequence variation. Projects are available (1) to help develop new methods in population genetics theory to draw inferences from data showing allele frequencies through time in experimental yeast populations, and (2) to conduct experimental evolution in budding yeast, evolving thousands of lines simultaneously to explore the distributions of phenotypic changes and their correlations with the evolution of genetic variation within and between populations.

John Calarco

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.

Rachel Dutton

Project 4. What are microbes doing in my cheese?!

Did you know that cheese is alive? Tiny, single-celled microbes are what give different cheeses their unique look, taste, and smell! But besides making cheese tasty, what else are these microbes doing? Are they talking to eachother (cell-cell communication) or competing with eachother for food? And how many different kinds (species) of microbes are there growing on a single piece of cheese?

In an effort to understand how microbes behave in complex environments, we are using cheese as a model. Summer interns would be involved in the study of cheese microbes and would utilize techniques such as DNA extraction, PCR, and culturing microbes in the lab. Interns would be involved in projects aimed at caracterizing the different types of microbes that grow on different cheeses, and study the interactions between species.

Andrew Murray

Project 5. Directing the evolution of plasmid 'species' in Escherichia coli

Plasmids, circular double stranded DNA molecules, are found in the majority of prokaryotic cells. They are classified into groups, or species, based on their ability to coexist within the same cell; those of the same species being incompatible with each other. The mechanism underlying compatibility is dictated in part by the particular segregation machinery encoded on the plasmid. This machinery ensures that when a bacteria cell divides, the mother and daughter cells faithfully obtain at least one copy of the plasmid. We have identified numerous sequences encoding segregation machinery from a diverse set of plasmids that exert strong incompatibility with each other, indicating that these plasmids belong to the same 'species'. The goal of this project is to evolve these incompatible plasmids to gain compatibility with each other through mutation of the segregation machinery, thus generating novel plasmid 'species'. The project will draw on basic microbiological techniques in handling and culturing bacterial strains, and extensive DNA manipulation. Incompatibility assays are fluorescence based and utilize fluorescence activated cells sorting (FACS) analysis and basic microscopy techniques. Additionally there is a mathematical component of this project, although a math background is not essential.

Project 6. Investigating the fitness effects of division of labor

Many multicellular organisms exhibit division of labor, i.e., the specialization of multiple cell types to perform tasks whose benefits are shared across the organism. To better understand the fitness effects conferred by division of labor, we are developing a model for cellular differentiation and aggregation in the budding yeast S. cerevisiae. Our goal is to demonstrate that introducing two cell types with distinct community-benefit functions can (a) provide a fitness advantage in a unicellular organism, and (b) produce a selective pressure favoring alleles that confer multicellularity. Depending on the candidate's interests, this project may involve cloning, flow cytometry, microscopy, experimental evolution, and/or computational modelling.

David Nelson/Andrew Murray

Project 7. Measuring competitive fitness on a surface

Microbes live in a wide variety of natural habitats, many of which are two-dimensional surfaces, such as rocks, plant leaves, teeth etc. The survival of a specific species or strain depends on its fitness relative to its competitors, an important parameter of evolutionary dynamics. The standard way to measure competitive fitness in the laboratory is a fitness assay in liquid culture. We have developed a simple assay to measure the fitness of yeast cells growing on an agar surface. In this assay, we extract the competitive fitness from the shape of the boundary of two colliding colonies using quantitative image analysis.

The goal of this project is twofold: The existing assay will be probed on other microbial species, and it will be extended towards observing and analyzing many colliding colonies simultaneously. This project employs basic laboratory techniques in culturing and handling microbes, in particular E. coli and S. cerevisiae. The surface fitness assay uses basic fluorescence microscopy and image analysis with the software program Matlab. While the focus of this project is on experiments and data analysis, modeling (i.e., simulating) the experiments may become part of the project depending on interest. While lab experience is not essential, experience with computer programming (not necessarily Matlab) is recommended.

Galit Lahav

Project 8. Dynamics and function of p53 in embryonic stem cells

The tumor suppressor p53 is a master regulator in the signaling network that provides protection against genomic instability. As the "guardian of the genome," p53 responds to cellular stress, including DNA damage, by triggering a variety of cell fate responses. Responses to DNA damage include repair, cell cycle arrest, senescence, and apoptosis. While our lab has shown that damage-induced p53 pulses in somatic cancer cells lead to cell cycle arrest, in embryonic stem cells the activity of p53 appears to trigger apoptosis. How this distinct cellular outcome is regulated by the same protein network is an open question. The aim of this research project is to assess the differences in level, activity, modification state, or localization of regulatory proteins in the p53 network between pluripotent stem cells and differentiated, non-pluripotent cells. Using live cell time-lapse fluorescence microscopy, immunofluorescence, and standard molecular biology techniques, we will probe how these differences in the signaling network contribute to the choice of cell fate.

Jeremy Gunawardena

Project 9. Information processing in mammalian signal transduction networks

The Gunawardena Lab is interested in how mammalian signal transduction networks process information and make decisions (http://vcp.med.harvard.edu/). We study this using a combination of experiments, computation and mathematical theory. On the experimental side we use microfluidic devices to subject cells to complex stimulations, immunostaining and fluorescence microscopy to measure protein states and in-vitro biochemistry, mass-spectrometry and NMR spectroscopy to probe reconstituted systems. We work mostly with cell lines and with mouse embryonic stem cells. On the mathematical side we use dynamical systems, algebraic geometry and Bayesian approaches to reconstruct and analyze networks of molecular interactions. We have a number of projects on the mathematical side that are suitable for short (two to three month) summer research internships. (Experimental projects may also be possible, depending on background and interest, but, typically, it is harder to make progress on these in a short time.) For instance, in post-translational modification of proteins, which is one of the key regulatory mechanisms in signal transduction, the geometry of the set of steady states provides considerable information about the underlying biochemical network that is responsible for the modifications (Biophys J, 95:5533-43 2008; Nature 460:274-7 2009; J Theor Biol 261:626-36 2009). We are using similar methods to study metabolic regulation in the Warburg effect in cancer and developmental patterning by gene regulatory networks. We are also studying calcium signaling, in which different mathematical techniques are being used to characterize the transient (ie: non-steady state) behavior of the underlying calcium signaling networks. We have a strong commitment to undergraduate research. Our students participate in current research projects and several have become authors on published papers, including some as first authors. Our group has a wide mixture of skills from cell biology and biochemistry to string theory and electronic engineering. If you have some mathematical background, a deep interest in modern biology and a willingness to work really hard for a couple of months, you could have a lot of fun.

Dan Needleman

Project 10: Evolutionary Biology of Cell Division

The architecture of cells and subcellular structures can show remarkable variability between tissues and organisms, but there is currently little understanding of the evolutionary basis of this diversity. Thus it is unclear why metaphase spindles in different Eukaryotes exhibit a range of morphologies and dynamics, or why the volumes of these spindles vary over one thousand fold. We have two projects to explore these issues: (1) We will use molecular tools to characterize the variations in sequence in proteins responsible for spindle structure and function which occur between and within species of nematodes. This work will give insight into the evolution and population genetics of cell division. (2) We will use experimental evolution to breed nematodes with altered developmental timing and cell size to see if such pressures drive changes in the cell division machinery. This work will test previously proposed hypothesis for the basis of variations in spindle structure and dynamics.

Roy Kishony

Project 11. The synthetic biology of synonymous codon usage

Every amino acid can be translated by multiple synonymous codons. This means that even for short protein sequences (50 amino acids) there can be very many (10^23) possible RNA sequences. Interestingly, different choices of synonymous codons have dramatic effects on protein expression and organismal fitness. We are looking for rules that predict how RNA sequences affect fitness and protein expression in cells. We will generate tons of data by screening synthetic DNA libraries for function using next-generation sequencing. This project will teach the latest in DNA synthesis and sequencing technology, as well as quantitative methods for analyzing large data sets. Previous experience with either molecular biology, iGEM or computer programming would be very helpful.

Michael Springer

Project 12. Evolution of signaling pathways in yeast

Signaling pathways can perform complex computations, but unlike man-made circuits, all biological networks had to evolve from other pre-existing networks. In order to understand how signaling pathways evolve and function, we are comparing cellular responses to changing environmental conditions in a number of related yeast species. Specifically, the project will involve creating yeast strains with fluorescent reporter constructs and monitoring the input-output relationship by flow cytometry and microscopy. The project will involve a mixture of experimental and computational work. Preference will be given to candidates with knowledge or experience in microbiology, programming, and quantitative methods.

Project 13. Yeast as a model organism for mitochondrial disorders

Mitochondrial disorders are some of the most prevalent inherited disorders. Although it can be challenging to determine the molecular basis for these disorders, several studies have successfully used yeast to elucidate human mitochondrial diseases. This is possible because approximately 600 mitochondrial genes found in yeast have human orthologs. This project will involve constructing a high-throughput system to replace deletions of yeast mitochondrial genes with human homologues to screen for new potential disease models by robotic growth measurements.

Philippe Cluzel

Project 14. Stress in Bacterial Lineages

What does it take to stress out E. coli? And, once a bacterium has been stressed, how long does it "remember" that stress? In this project we will expose E. coli to short bursts of chemical stress in aspecially designed microfluidic device and characterize the resulting changes in gene expression. We will then look for correlations in time and across generations. For example, if the mother cell responds strongly to the stress, is the daughter more likely to respond? How about the granddaughter? This project would be ideal for someone who likes to work with their hands. Your time would be divided between making improvements to our microfluidic device, microscopy experiments, image analysis with MatLab, and developing the fluorescent bacterial strains necessary for the experiment. If you'd like to see a movie of our microfluidic device in action, go to http://www.mcb.harvard.edu/Cluzel/movies.php