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Undergraduate Summer Research Internships
The Systems Biology community at Harvard invites interested undergraduates who will not have graduated by June 2010 to apply for research internships in the summer of 2010. The application deadline is February 16 (please note that this is also the deadline for receipt of the reference letters, which means that students need to upload their material beforehand to give their referees some time to upload their letters of recommendation). Starting on Monday June 7 the internship will last for ten weeks (until Aug 13). 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. Intern 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 alternative housing, for example organized through PRISE). Harvard students should 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 5 projects which are listed below. In your research statement please specify for which project(s) you are applying and why you are particularly interested in those projects. This description plays an important part in the selection process. You will also be asked to provide contact information for two referees who will be contacted automatically to submit their confidential recommendation letter. Ideally, the referees should know you from prior or current academic or research activities. 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 by February 16. 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 2010 1.Bugs and Drugs 2. Heliconius phylogeography and the evolution of mimicry 3. Molecular evolution of genes associated with butterfly evolution 4. Genetics of ladybug color patterning
5. Breeding a disease-causing misfolded protein 6.Bacteriophages and conjugation Project 7, Suckjoon Jun
8. Dyamics of degradation of the tumor suppressor p53 9. Chromosome segregation: ensuring faithful separation of genetic material at cell division 10. Evolving novel plasmid segregation mechanisms in bacteria 11. Cell fusion in yeast 12. Custom-built gene networks in human cells
14. Physical Biology: Probing Cytoskeletal Self-Organization With Computational Microscopy Project 15, Jeremy Gunawardena
16. Evolution of gene regulation in fruitflies 17. Synthetic morphogenesis in zebrafish 18. Signal integration in embryonic stell cells 19. Bacterial evolution in dynamic fitness landscapes
Project 1. Bugs and Drugs
Applicants with experience in microbiology and standard molecular biology techniques (e.g. cloning, DNA/RNA extraction, and PCR) are recommended, but not required. See turnbaugh.openwetware.org for more info.
We use butterflies and other insects as a model system to study the evolution and genetics of adaptation and speciation. We are looking for three motivated, energetic, and hard-working summer interns to work with us on exciting projects currently underway in the lab. Knowledge of basic genetics and previous lab experience would be helpful for these projects but they are not required. Please see the following website for more details: Kronforst lab Project 2. Heliconius phylogeography and the evolution of mimicry Heliconius butterflies are a premier example of adaptation by natural selection - species in this group have repeatedly evolved the same warning patterns across the neotropics leading to interspecific mimicry. We are using DNA sequence data to infer the age and geographic origin of this diversification. The summer intern for this project will generate and analyze DNA sequence data and quantify wing color patterns. This project will entail DNA extraction, PCR amplification, DNA sequencing, and quantitative wing image analysis. Project 3. Molecular evolution of genes associated with butterfly mimicry North American tiger swallowtail butterflies have a wing color polymorphism that generates mimicry of a distantly-related swallowtail model. We are just beginning to understand which genes may contribute to this color pattern variation. The summer intern for this project will expand preliminary DNA sequence datasets and then use these data to test whether specific candidate genes have experienced recent natural selection. This project will entail DNA & RNA extraction, PCR and RT-PCR amplification, DNA sequencing, and DNA sequence data analysis. Project 4. Genetics of ladybug color patterning The Multicolored Asian Ladybeetle, Harmonia axyridis, displays massive variation in color and pattern but previous analyses suggest that this variation is the result of a single, unidentified gene. We are working toward identifying this gene and the summer intern for this project will assist with this effort by raising experimental families of ladybugs and cloning portions of candidate genes. This project will entail collecting live ladybugs from around Boston, setting up experimental matings, rearing offspring, and using various molecular methods such as PCR amplification and DNA sequencing.
Project 5. Breeding a disease-causing misfolded protein Pathological protein misfolding ravages cells, creating the toxic molecular species that cause Alzheimer's, Huntington's, Parkinson's, ALS, and most dementias, among other diseases. Why misfolded proteins are toxic remains poorly understood; one possibility is that they evade degradation by cleanup enzymes long enough to wreak havoc on cellular machinery like so many molecular wrenches. To understand how, and how much, misfolding harms cells, we have created an artificial protein misfolding disease in baker's yeast, a simple model organism which is easy to genetically manipulate. This disease, which slows the growth of yeast cells in a way that would be devastating over evolutionary time, stems from the disrupted folding of molecules of a mutant yellow fluorescent protein (YFP). We'd like you to breed (by mutation and selection) misfolded YFP proteins that evade degradation for much longer than this first mutant YFP, to test the prediction that toxicity is linked to the amount of time the misfolded protein has to work its mischief. In other words, can you breed an acute protein misfolding disease-causing molecule? Strong candidates will have previous laboratory experience (not required) and clear motivation to get to the bottom of a very basic cellular mystery (required).
Irene Chen
For more information, see http://www.sysbio.harvard.edu/csb/jun
The tumor suppressor protein, p53 controls essential cellular stress responses and its malfunctioning is strongly linked to tumorigenesis. p53 exerts its functions both acting as transcription factor and via protein-protein interaction. It has a wealth of targets and cofactors that form a vast and intricate protein network, part of which are better characterized than others. The activation of the p53 protein network is triggered by a number of different stresses and it produces an effective response tailored to the upstream signal. Our lab studies the in vivo dynamics of the p53 network after DNA damage, using live cell imaging, time-lapse fluorescence microscopy, immunofluorescence, mathematical modeling and standard molecular biology techniques. The function of p53 is controlled mainly at the protein level, through post-translational modifications and co-factor binding. While the level of p53 translation is relatively constant, its degree of sensitivity to degradation regulates the total p53 levels. The internship project will focus on studying the dynamics of degradation of p53 both from a theoretical and experimental standpoint. A mathematical model will be written, solved and used to assess the key features of p53 degradation reaction and its dynamics. The results from the theoretical study will be used to design suitable experiments to probe the degradation pathway in vivo. The ultimate goal would be to interface back and forth between theoretical model and experiments to investigate how the rate of p53 degradation affects its levels and dynamics in response to DNA damage and how defects in the proper regulation of p53 degradation might affect its function and lead to cancer formation.
Project 9. Chromosome segregation: ensuring faithful separation of genetic material at cell division One of our lab’s goals is to elucidate the mechanism by which cells faithfully segregate their genetic material during cell division. Chromosomes must be separated with each mother and daughter cell receiving one of the copies, or chromatids; mistakes in this process can lead to aneuploidy, a hallmark of cancer and birth defects. In order to ensure equal segregation, chromatids must be attached to microtubules emanating from opposite poles of the dividing cell, thus allowing them to be separated and pulled into the two new cells. The attachment of chromatids to the microtubules of the mitotic spindle is a chaotic process with the possibility of incorrect attachments; yet cells are able respond to such mistakes and delay division until all chromosomes are properly attached to the spindle. How do cells sense incorrectly attached chromosomes and distinguish them from correctly attached ones? This project seeks to answer this fundamental question. Using the model organism S.cerevisiae, you will investigate whether cells use tension as a signal for distinguishing between correctly and incorrectly attached chromosomes. The project involves artificially tethering chromatids together and characterizing cell division rates and chromosome loss rates. Applicants should have a background in molecular and cellular biology and previous lab experience is beneficial but not required. Enthusiasm to learn is the most important qualifier! Project 10. Evolving novel plasmid segregation mechanisms in bacteria When a bacteria cell divides, both daughter cells faithfully obtain at least one copy of an endogenous plasmid. This is mainly due to the presence of segregation machinery encoded by the plasmid DNA. We focus specifically on the well characterized machinery that is encoded on the R1 plasmid from Salmonella enterica. Homologs of this system exist on a diverse set of plasmids from numerous bacterial species. The sequence identity between the homologs and R1 is very poor and virtually nothing is known about their mechanism. It will be the first goal of this project to determine the extent at which some of these homologs share similar segregation mechanisms to that of the R1 plasmid. To achieve this we will exploit a phenomenon known as plasmid incompatibility. When a bacterial cells contains two plasmids with the same segregating machinery, there is a high propensity for the cell to loose one or other of these plasmids over time. Therefore by determining how incompatible a plasmid encoding a homologous sequence is with an R1 plasmid we will gain an insight into how similar their segregation mechanisms are. The second goal of the project will be to evolve two previously incompatible plasmids to gain compatibility through mutation of the segregation machinery. The results of both these goals will illuminate the specific DNA sequences that govern the mechanism with which plasmids segregate. The project will draw on basic microbiological techniques in handling and culturing bacterial strains. Incompatibility assays are fluorescence based and utilize fluorescence activated cells sorting (FACS) analysis and basic microscopy techniques. Project 11. Cell fusion in yeast Cell fusion is an important event in the life cycle of many organisms including fertilization of an egg by sperm, formation of various cell types in animals, and in the life cycle of algae and fungi. Perhaps the simplest and most well studied form of cell fusion is mating of the budding yeast, Saccharomyces cerevisiae, where two haploid yeast cells fuse to form a single diploid cell. A yeast cell has both a cell wall and cell membrane. Cells cannot mate until they have dissolved their cell walls and allowed their membranes to touch each other and fuse. This is a dangerous moment: if the cell dissolves its cell wall in a region where it is not contacting a mating partner, water rushes in and the cell explodes. Our lab is interested in determining what causes the cell to dissolve its cell wall during mating and how the cell controls which parts of the wall are broken down. Although many genes have been implicated in S. cerevisiae mating, it may be necessary to identify more genes in order to determine the trigger that causes the dissolution of the cell wall. Your project will focus on finding genes involved in cell wall breakdown during mating by screening the yeast deletion collection, a systematic deletion of non-essential genes in the yeast genome, for mating mutants and then following up on these using microscopy and quantitative mating assays. Techniques used will include basic yeast genetics, fluorescence microscopy, and molecular biology. Project 12. Custom-built gene networks in human cells Gene regulators function within networks that are reminiscent of electronic circuit boards. Promoters, DNA binding motifs, activators, repressors, etc. work in concert to determine when and how genes are expressed. What happens when we extract parts (DNA and proteins) from nature to assemble a custom-made gene circuit? Can such a circuit predictably function in human cells? Our lab uses synthetic biology to assemble DNA sequences into artificial gene networks, we introduce these into cultured human cells, then observe how the network is expressed via fluorescent proteins produced as output by the circuit. The project presents opportunities to investigate artificial gene circuit behavior in human cells, model circuit behavior using MATLAB, and explore how chromatin (the protein-DNA complex) can be used in an artificial circuit. The intern will gain experience with human/ mammalian cell culture, gene expression assays, computer modeling, cytology, and standard molecular cloning techniques. The successful candidate will have experience with standard molecular cloning techniques and a solid background in, and strong enthusiasm for, molecular and cell biology. Project 13. Evolutionary Cell Biology: Theoretical Analysis of Evolutionary Forces Shaping Cytoskeletal Organization In this project we will attempt to gain insight into the evolutionary forces that determine the structure of the spindle by combining a comparative analysis of results available in the literature with phenomenological and population genetic theories. Such an analysis should help to determine how selection, neutral drift, and biophysical constraints conspire to produce subcellular organization. This work will require assembling a database of the architecture of spindles from different organisms, extracting quantitative information from this data, and using computer simulations to test different models of the evolution of the spindle. In addition, we may use approaches from bioniformatics to investigate the evolution of the molecules that make up the spindle. This project requires a highly motivated individual who is willing to work independently. A number of different directions are possible based on the interests of the intern. Experience with computer programming is required. Project 14. Physical Biology: Probing Cytoskeletal Self-Organization With Computational Microscopy A wide variety of subcellular assemblies exist in a non-equilibrium steady state with a constant flux of molecules and energy continuously modifying and maintaining their architecture. A prime example of this is the spindle: a remarkable, self-organizing structure that segregates chromosomes during cell division. While traditional approaches are giving increase insight into the molecules which make up the spindle, we still do not understand how these constituents work together to produce large-scale, biologically relevant behaviors. In this project, we will attempt to gain insight into physical aspects of cytoskeletal organization using a combination of computer simulations and light microscopy. We will test a framework designed to rigorously establish what information can be extracted from experimental data when studying steady-state, non-equilibrium structures like the spindle. This project requires a highly motivated individual who is willing to work independently. A number of different directions are possible based on the interests of the intern. Experience with computer programming is required. Project 15. Information processing in mammalian signal transduction networks Project 16. Evolution of gene regulation in fruit flies Project 17. Synthetic morphogenesis in zebrafish In this project, we are interested in building a synthetic circuit to turn a sheet of cells into a finger-like projection. It is unknown how cell behavior is precisely coordinated within a tissue to determine the shape and size of an organ. In the developing vertebrate ear, a sheet of cells is remodeled and expands at particular locations as finger-like projections. Like E.T.’s finger reaching out to Elliot’s finger, the projections grow across the hollow interior of the developing ear vesicle to meet and fuse with a similar projection growing from the opposite side of the ear. The resulting pillars define the semicircular canals, an organ involved in how we sense our body’s spatial orientation and balance. It is unclear how growth, shape, and guidance of projections works, but zebrafish genetics suggests several possible mechanisms may be important. We will engineer a memory device to be triggered by regionally defined application of a microscope’s laser to elevate and sustain production of morphogenetic actuators. If this synthetic devise allows us to control the growth of projections we will also be able to ask basic questions in developmental biology concerning tissue guidance and epithelial fusion. The project will give you experience in synthetic biology, zebrafish genetics, vertebrate physiology, injecting and staging of embryos, developmental biology, confocal microscopy, and quantitative image analysis. Project 18. Signal integration in embryonic stem cells Pluripotent embryonic stem cells have the potential to give rise to any of the multiple cell types in the adult body. We are interested in finding out how these cells integrate external signals to make the appropriate developmental decisions, as they differentiate into a particular cell type. The summer project will involve learning how to make transgenic mouse embryonic stem cell lines, following expression of multiple factors within these cells as they differentiate into different mesendodermal tissue types, image processing to extract quantitative data, and analysis of the data. The interested students should have prior molecular biology and cloning experience, or should be adept in using mathematical techniques at the advanced undergraduate level as well as programming. Project 19. Bacterial Evolution in Dynamic Fitness Landscapes
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