Dynamics of double-strand break repair


In a new paper in the journal Genetics, former Brandeis postdoc Eric Coïc and undergrads Taehyun Ryu and Sue Yen Tay from Professor of Biology Jim Haber’s lab, along with grad student Joshua Martin and Professor of Physics Jané Kondev, tackle the problem of understanding the dynamics of homologous recombination after double strand breaks in yeast. According to Haber,

The accurate repair of chromosome breaks is an essential process that prevents cells from undergoing gross chromosomal rearrangements that are the hallmark of most cancer cells.  We know a lot about how such breaks are repaired.  The ends of the break are resected and provide a platform for the assembly of many copies of the key recombination protein, Rad51.  Somehow the Rad51 filament is then able to facilitate a search of the entire DNA of the nucleus to locate identical or nearly identical (homologous) sequences so that the broken end can pair up with this template and initiate local copying of this segment to patch up the chromosome break.  How this search takes place remains poorly understood.

The switching of budding yeast mating type genes has been a valuable model system in which to study the molecular events of broken chromosome repair, in real time.  It is possible to induce synchronously a site-specific double-strand break (DSB) on one chromosome, within the mating-type (MAT) locus.  At opposite ends of the same chromosome are two competing donor sequences with which the broken ends of the MAT sequence can pair up and copy new mating-type sequences into the MAT locus.

Normally one of these donors is used 9 times more often than the other.  We asked if this preference was irrevocable or if the bias could be changed by making the “wrong” donor more attractive – in this case by adding more sequences to that donor so that it shared more and more homology with the broken ends at MAT.  We found that the competition could indeed be changed and that adding more homologous sequences to the poorly-used donor increased its use.


In collaboration with Jané Kondev’s lab we devised both a “toy” model and a more rigorous thermodynamic model to explain these results.  They suggest that the Rad51 filament carrying the broken end of the MAT locus collides on average 4 times before with the preferred donor region before it actually succeeds in carrying out the next steps in the process that lead to repair and MAT switching.

Dynamics of homology searching during gene conversion in Saccharomyces cerevisiae revealed by donor competition Eric Coïc , Joshua Martin, Taehyun Ryu, Sue Yen Tay, Jané Kondev and James E. Haber. Genetics. 2011 Sep 27 2011 Sep 27

New Computational Neuroscience Training Program

The National Institute on Drug Abuse has recently awarded Brandeis a pair of linked training grants to support student training in computational neuroscience. The program is unusual for NIH training grants in supporting both undergraduate and graduate student research. Funding for the program is approximately $1.8 million over the next five years.

Modeling a biconditional discrimination task, see Bourjaily & Miller, 2011

The program, directed by Professor Eve Marder, will support six Ph.D. students and six undergraduates (juniors or seniors) each year. Students must be working to fulfill an appropriate degree in the Division of Science at Brandeis, and must engaged in research in computational neuroscience. Said Marder,

We are extremely pleased to have received this grant, as it continues a long Brandeis tradition of integrating theory and experimental work in the neurosciences.  We are especially pleased to have the undergraduate component, as we know there are students who are interested in learning how to employ rigorous quantitative methods to study the brain.

Eligibility and program requirements to participate in the program will soon be available at the training grant website.

Some recent publications:

Bourjaily, M.A., and Miller, P. (2011). Synaptic plasticity and connectivity requirements to produce stimulus-pair specific responses in recurrent networks of spiking neurons. Plos Comput Biol 7, e1001091.

Piquado, T., Cousins, K.A., Wingfield, A., and Miller, P. (2010). Effects of degraded sensory input on memory for speech: Behavioral data and a test of biologically constrained computational models. Brain Res 1365, 48-65.

Berkes, P., Orban, G., Lengyel, M., and Fiser, J. (2011). Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment. Science 331, 83-87.

Grashow, R., Brookings, T., and Marder, E. (2010). Compensation for variable intrinsic neuronal excitability by circuit-synaptic interactions. J Neurosci 30, 9145-9156.

Postdoc with confessed aversion to genetics

“… now inspiring a new generation of neurophysiologists”

There’s a nice story on the ADInstruments website about Stefan Pulver (PhD ’09) and Nick Hornstein (’11) and the tools they developed in the Griffith lab for “Optogenetics in the Teaching Laboratory” using Drosophila and channelrhodopsin-2. Stefan is currently in Cambridge (England) doing a postdoc, and Nick is starting his MD/PhD at Columbia real soon now.

Brandeis Summer SciFest to be held on Aug 3

Brandeis Summer Scifest, an Undergraduate Research Poster Session, will be held on Wed, Aug 3 2011.   53 undergraduate students from across the Division of Science, including summer visitors and Brandeis students, will present posters on their work/research.  The poster session will run from 1-3 pm in the Shapiro Science Center atrium.

The public is cordially invited to attend and to discuss research with the students.

A listing of poster titles and abstracts is available at http://www.bio.brandeis.edu/UG/scifest-2011.pdf


Aug 4: The poster session went really well, we had a nice turnout and the students did a great job presenting.

Photo by Emma Griffith

Physics students present research at 20th Annual Berko Symposium on May 16

On Monday, May 16, the Physics Department will hold the Twentieth Annual Student Research Symposium in Memory of Professor Stephan Berko in Abelson 131. The symposium will end with talks by the two Berko Prize winning students, undergraduate Netta Engelhardt and graduate student Tim Sanchez. The whole department then gathers for a lunch of cold cuts, cookies and conversation. “It’s a great way to close out the academic year,” said Professor of Astrophysics and Department Chair John Wardle. “We come together to celebrate our students’ research and hear what the different research groups are doing.”

The undergraduate speakers will describe their senior thesis honors research. This is the final step in gaining an honors degree in physics, and most of them will also be co-authors on a paper published in a mainline science journal. The graduate student speakers are in the middle of their PhD research, and will disucss their progress and their goals.

The prize winners are nominated and chosen by the faculty for making particularly noteworthy progress in their research. Graduate student winner Sanchez’ talk is titled “Reconstructing cilia beating from the ground up.” He works in Professor Zvonimir Dogic’s lab studying soft condensed matter. Undergraduate winner Engelhardt’s talk is titled “A New Approach to Solving the Hermitian Yang-Mills Equations”. She works with Professors Matt Headrick and Bong Lian (Math) on problems in theoretical physics and string theory. The schedule for Monday morning and abstracts of all the talks can be found on the Physics Department website.

Sanchez’ research very much represents the growing interdisciplinary nature of science at Brandeis. Here, a physicist’s approach is used to study a biological organism. Professor Zvonimir Dogic says of his work “He has made a whole series of important discoveries that are going to have a measurable impact on a number of diverse fields ranging from cell biology, biophysics, soft matter physics and non-equilibrium statistical mechanics.  His discoveries have fundamentally transformed the direction of my laboratory and probably of many other laboratories as well.”

Engelhardt’s research is much more abstract and mathematical, and concerns fundamental problems in string theory, not usually an area tackled by undergraduates. Professor Headrick says “Netta really, really wants to be a theoretical physicist, preferably a string theorist. She has a passion for mathematics, physics, and the connections between them.” He adds that she is utterly fearless in tackling hard problems. Netta has been awarded an NSF Graduate Research Fellowship based on her undergraduate work here.  Next year she will enter graduate school at UC Santa Barbara and will likely work with eminent string theorist Gary Horowitz, who has already supervised the PhD research of two other Brandeis physics alumni, Matthew Roberts ’05, and Benson Way ’08.

This Student Research Symposium is now in its 20th year. The “First Annual…..” (two words which are always unwise to put next to each other) was initiated in 1992 by Wardle to honor Professor Stephan Berko, who had died suddenly the previous year. Family, friends and colleagues contributed to a fund to support and celebrate student research in his memory. This provides the prize money which Netta and Tim will share.

Stephan Berko was a brilliant and volatile experimental physicist who was one of the founding members of the physics department. He was born in Romania in 1924 and was a survivor of both the Auschwitz and Dachau concentration camps. He came to the United States under a Hillel Foundation scholarship and obtained his PhD at the University of Virginia. He came to Brandeis in 1961 to establish a program in experimental physics and worked tirelessly to build up the department. Together with Professors Karl Canter (dec. 2006) and Alan Mills (now at UC Riverside) he established Brandeis as a world center for research into positrons (the anti-matter mirror image of ordinary electrons). In a series of brilliant experiments they achieved many “firsts,” culminating in election to the National Academy of Sciences for Steve, and, it has been rumored, in a Nobel Prize nomination for the three of them. Steve was as passionate about teaching as he was about research, and when he died, it seemed most appropriate to honor his memory by celebrating the research of our graduate and undergraduate students. During the coffee break on Monday, we will show a movie of Steve lecturing on “cold fusion,” a headline-grabbing but phony claim for producing cheap energy from 1989.

Beckman Scholarships and URP Awards for Summer 2011

Beckman Scholars and Undergraduate Research Program Winners

Summer 2011

Beckman Scholars

The 2011 Beckman Scholars are:

Frank Scangarello (mentor: Suzanne Paradis, Biology)
Multivalent Metalloproteases Inhibitors to Increase Small Molecule Avidity and Selectivity to Study Semaphorin4D-Cleavage Mediated Synaptic Nerve Development

Zhequan Xu (mentor: Christine Thomas, Chemistry)
Novel Catalyst Design for Green Fuels

URP Recipients

(only students from the Division of Science are included in this list)

Heather Bernstein ’12 (Language & Linguistics; Neuroscience) with Prof. Stephen Van Hooser
Stimulus Therapy & its Implications for Rehabilitation: Using Channelrhodopsin-2 to determine spike time-dependent plasticity in neurons of the primary visual cortex in postnatal ferrets at eye opening

James En Wai Chin ’14 (Chemistry) with Prof. Lizbeth Hedstrom
IMP dehydrogenase nucleic acid association (How do IMPDH mutants affect IMPDH nucleic acid binding?)

Nimrod Deiss-Yehiely ’12 (Biology) with Prof. Sacha Nelson
A mouse model for Infantile Spasms involving TTX

Scott Finkelstein ’12 (Biology) with Prof. Paul Miller
Comparative Success of Strategies in a Continuous Iterated Prisoner’s Dilemma

Jessica Friedman ’13 (Biochemistry) with Prof. Tom Pochapsky
Insights into Substrate Recognition in Cytochrome P450cam

Julie Miller ’12 (Neuroscience) with Prof. Stephen Van Hooser
Roles of Inhibitory Neurons in Cortical Development

Anna Slavina ’12 (Psychology) with Prof. Art Wingfield
Selective syntactical attention among bilingual speakers

Sophie Travis ’13 (Biochemistry) with Prof. Dagmar Ringe
In vitro characterization of VPS35

Akash Vadalia ’12 (Biology; HSSP) with Prof. Angela Gutchess
Cross-Cultural Differences in the Specificity of Memory for Objects and Contexts

Alison White ’13 (Psychology) with Prof. Art Wingfield
Monitoring the Capacity of Short Term Memory

Abigail Zadina ’13 (Psychology) with Prof. Michael Rosbash
Huntington’s Disease: Insights into Mechanisms Involving Circadian Systems

Biochemistry Senior Research Talks on April 29

The Department of Biochemistry presents senior research talks by the 2010/2011 Biochemistry Honor and BS/MS Candidates on Friday, April 29, 11:30-1:30pm in Gerstenzang 121.

Benjamin D. Hornstein – BS/MS
Seq A: construction and analysis of mutants
Advisor: Sue Lovett

Marcus R. Kelly- BS/MS
Replacement Matrices for Transmembrane Proteins
Advisor: Douglas Theobald

Yuliya Y. Mints – BS/MS
Inosine Monophosphate Dehydrogenase and Transcription: a mechanism for retinitis pigmentosa?
Advisor: Liz Hedstrom

Sarah Naomi Olsen – BS/MS
Isolation, Purification, and Characterization of (+)-4R-limonene synthase
Advisor: Dan Oprian

Benjamin M. Whitlock – BS/MS
PABPN1 and SKIIP: A putative mechanism for the onset of Oculopharyngeal Muscular Dystrophy
Advisor: Dagmar Ringe

Philip D. Lessans – BS
Developing a Method of Extracting Native U snRNPs from eukaryotic cells using Snurportin 1 constructs
Advisor: Daniel Pomeranz Krummel

Jessica P. Liken – BS
Deletion Library Screen for Enhancers and Suppressors of ALS-associated FUS/TLS Toxicity in Yeast
Advisor: Greg Petsko

Everyone is welcome and encouraged to come. Pizza will be provided.

Two more NSF GRFP fellowship winners

Brandeis had 1 current undergraduate, 7 undergraduate alunmi, and 1 incoming graduate student win NSF graduate research fellowships this year. In addition to those cited below, Richard Stefan Isaac ’10 and Orly Wapinski ’09 were also selected. Isaac graduated magna cum laude with a BS/MS degree with high honors in Biochemistry. His thesis work “Functional Characterization of Regulators of Bacterial Pathogenicity and
Metabolism
” was done in the Petsko/Ringe lab. His work teaching in the Biology laboratory also resulted in a paper  in CBE Life Science Education. Isaac is currently a graduate student at Univ. of California, San Francisco. Wapinsky received a BS degree with Highest Honors in Biology, doing in her thesis work “Characterization of Interferon Regulatory Factor-4 mutants” with Professor Ruibao Ren. Wapinski is currently studying at Stanford.

Daniel Graham ’10, and Aaron Gell ’10, and Jeffrey Dobereiner ’09 awarded 2011 NSF Graduate Research Fellowships

Former chemistry majors Daniel Graham ’10, Aaron Gell ’10, and Jeffrey Dobereiner ’09 have been awarded National Science Foundation Graduate Research Fellowships. These Fellowships, geared towards ensuring the vitality of the country’s scientific workforce, support the graduate education of individuals who have demonstrated their potential for significant achievements in scientific research.  Dan and Aaron are currently first year graduate students at MIT, pursuing Ph.D.s in inorganic chemistry.  Dan received highest honors in chemistry for thesis research conducted in the lab of Professor Christine M. Thomas, and is currently continuing to investigate chemical approaches to renewable energy strategies in the lab of Professor Daniel Nocera at MIT.  Aaron, also an inorganic chemist, conducted undergraduate research in the Brandeis chemistry department under the supervision of Professor Bruce Foxman. Jeff was a double major in anthropology and chemistry at Brandeis and is currently pursuing a Ph.D. in Archaeology at Harvard University, where he is applying his chemistry knowledge to the analysis of ancient artifacts. In addition, Delora Gaskins, a 2011 incoming graduate student in the area of physical chemistry, was awarded an NSF Fellowship.  Delora is completing her undergraduate degree at Cal. State. – Long Beach and hopes to join the lab of Professor Irving Epstein in the fall of 2011.

Keith Cheveralls ’09, Daniel Beller ’10, and Netta Engelhardt ’11 awarded NSF Graduate Research Fellowships

Former physics majors Keith Cheveralls ’09 and Daniel Beller ’10 and current physics major Netta Engelhardt ’11 have been awarded the prestigious National Science Foundation Graduate Research Fellowship. The fellowship recognizes and supports outstanding graduate students in the US who have demonstrated exceptional promise in science research. Keith is currently a first year graduate student at UC Berkeley; while at Brandeis he did his senior thesis with Professor Jane Kondev and was a co-author on a paper that appeared last year in the Proceedings of the National Academy of Sciences. Dan, a first year graduate student at the University of Pennsylvania, completed his senior thesis at Brandeis with Professor Zvonimir Dogic and Professor Robert Meyer.  Currently, Dan is conducting research on liquid crystals in the group of Professor Randall Kamien at UPenn. Netta is currently doing her senior thesis with Professor Matthew Headrick, and is planning to attend graduate school in physics next year.

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