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

Susan Birren named Dean of Arts and Sciences

Brandeis President Frederick Lawrence today announced via e-mail that Professor of Biology Susan Birren will be the next Dean of Arts and Sciences. According to Lawrence’s e-mail:

An internationally recognized researcher in developmental neurobiology who studies how developing nerve cells respond to the local environment to create the nervous system, Susan is affiliated with the National Center for Behavioral Genomics and the Volen Center for Complex Systems.

Susan is a distinguished scholar, an experienced academic leader and a talented educator. She has the wisdom to promote what is essential to each of the disciplines in the Arts and Sciences while working closely with each of the four schools, the different groups within the schools, and across disciplinary boundaries.

For more, see the story at Brandeis NOW

 

Biology mentors and mentees needed

The Biology Undergraduate Peer Mentorship Program is a new initiative by the Biology Department and was created by Biology UDR, Dipal Savla. In the program, junior and senior Biology mentors will provide guidance to freshmen and sophomores mentees who are considering majoring in Biology. Oftentimes, new biology majors have a broad range of concerns such as what courses to take, when to take them, how to get involved in research, selecting and applying to internships and other experiential opportunities, and balancing the biology major with other academic and extracurricular interests. Through the program, mentors will be able to use their experience as Biology majors to help mentees work towards their goals as early as the first day of their freshman year. The specifics of the mentor-mentee relationship are flexible — Mentors and mentees can communicate over email or meet in person depending on what they decide.

The program was created in response to the diverse range of interests students have within the biology major. For example, students who are double majoring in Biology and Neuroscience have very different goals for their biology major than students double majoring in Biology and Environmental Studies. Thus, they would have differing choices for courses and internships. The students best able to advise these students would be those who have worked through similar issues.

If you are a rising freshman or sophomore considering a major in biology, and would like to join this program as a mentee, please email Dipal Savla (dsavla@brandeis.edu) for more information and an application.

Undergraduate Biology Lab Students All Get Cataracts

After a series of renovations and modifications, the fall semester of introductory biology (Biol18b) is now an 11 week project-based lab course focused on Molecular and Structural Biology.  Students in the course now design their own mutant of γD crystallin (a human protein implicated in congenital and age-onset cataractogenesis) using site-directed mutagenesis, purify and express their protein, and then study its stability using fluorescence and AFM.

A new paper in CBE – Life Sciences Education by Brandeis undergraduates Dan Treacy, Rebecca Miller, Stefan Isaac, Danielle Saly, and Saumya Sankaran, together with grad student Susannah Gordon-Messer and Assistant Professor of Biology Melissa Kosinski-Collins,  discusses a two-year study focused on assessing both student perception of the course and analyzing the levels conceptual understanding and knowledge retention of participants.  This paper marks the second in a series of articles highlighting studies performed by life science undergraduates enrolled in an educational internship course (Ed92a) with Kosinski-Collins.

Biology research experiences at Brandeis (Summer 2011)

Thanks to new funding from the National Science Foundation, starting in Summer 2011 Brandeis will offer a new research experiences for undergraduates (REU) program in Cell and Molecular Visualization. This new grant, organized by principal investigator Susan Lovett, will provide funding for 10 undergraduates to spend 10 weeks at Brandeis in the summer doing independent research projects in close collaboration with faculty mentors. NSF REU programs place special emphasis on providing research opportunities for under-represented groups in science, and for students whose colleges cannot provide cutting-edge research facilities.

The new program will join Brandeis’s  existing MRSEC REU and other summer research activities in providing a lively atmosphere for young researchers. This competitive program will provide stipends of $5000 each plus housing and meal allowances. Participants must be US citizens or permanent residents, and should have completed their sophomore or junior year of study and be enrolled in an accredited undergraduate college or university. Further information including an application form is available on the Biology website.

Being given the opportunity to do research as an undergrad was amazing, fun, intellectual, and extremely useful; I’ve done it for two summers now.   At the beginning of my college career I was pre-med, but it only took a summer of research to help me realize that I actually want to do science over the course of my career […]

(see more quotes from undergraduates about summer research)

Biology study abroad

The Biology Dept. and the Office of Study Abroad will hold a joint presentation about studying abroad as a Biology major at 3:30pm on Tuesday, March 8 in the Alumni Lounge in Usdan Student Center (event listing on facebook). Come and learn about the many study abroad programs available, how you can fit study abroad into your schedule, and the exciting places you can go!

There will be presentations from J. Scott Van Der Meid, the Director of Study Abroad, Dr. Dan Perlman, the Biology Department Study Abroad Liaison, and Dr. Joan Press, the Biology Undergraduate Advising Head. Students will also get the chance to ask talk to Biology majors who have studied abroad in the past, and learn how their experiences have enhanced their academic experience at Brandeis.

Hope to see you all there!

Biology UDRs

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