Dr. James Haber is to be named the 2011 Thomas Hunt Morgan medal recipient

Much like the scientist after whom this prestigious award is named,  Jim Haber has spent his scientific career asking big questions about genetics with the help of a small organism.  Instead of the humble fruit fly employed by Thomas Morgan, Jim and his students use the even humbler baker’s yeast Saccharomyces cerevisiae to study the complicated mechanisms of DNA recombination and repair.

Angie Brooksby (www.atelierfige.com)

Packed inside each little yeast cell is approximately 6000 genes worth of DNA, and the cell’s molecular machinery works very hard to fix any mistakes that might get incorporated into the genetic code.  Such mistakes can be caused by ultraviolet irradiation, mutagenic chemicals, and may even arise during the process of DNA replication itself.  Understanding how the yeast cell copes with these blows to its genetic integrity, as well as the consequences of mistakes gone unfixed, has been the focus of the Haber lab for over 20 years– but you don’t have to take my word for it.

In addition to recognizing purely scientific accomplishments, the Thomas Hunt Morgan medal is awarded to scientists who have proven to be excellent mentors to the students they work with.  In the spring of 2008, former students and post-docs of the Haber lab gathered at Brandeis to participate in a symposium honoring Jim’s 60th birthday, and the turn-out made clear that a sizeable amount of those who worked with Jim have either gone on to start successful labs of their own or entered into post-doctoral positions in labs of good repute.

When asked to reflect on what it’s been like to work with Jim, recent Haber lab graduate Dr. Wade Hicks answered that Jim “was a great mentor for me because he was always available to listen and talk about science.”  When further pressed against the journalistic blade and asked if Jim hosts any great parties, Wade coughed up that  “[Jim] does host the annual Halloween/pumpkin carving party that all the lab members’ kids enjoy…  What’s better than pumpkins, large knives, kids, and alcoholic beverages!?”

And finally, Jim’s eager willingness to talk about science extends beyond his lab and into the larger Life Sciences community– and likely beyond that.  Graduate students at departmental social events would be wise to chat Jim up regarding their projects– not to mention their gardens, favorite books, wine recommendations, etcetera.  In addition to being a great scientist, Jim is an all-around Good Guy.

Congratulations, Dr. Haber!

For further press see:

The Justice

Brandeis NOW

Connecting with underrepresented minorities in the sciences

For the past six years, Brandeis has been participating yearly at two undergraduate-oriented conferences in an effort to recruit the best minority students for the life sciences graduate programs. These two conferences are: SACNAS (Society for advancing Hispanics/chicanos and Native American in science) and ABRCMS (Annual Biomedical research conference for minority students).

This year SACNAS was held at Anaheim, CA during September 30 and October 3. Professor Jim Morris and 2 graduate students represented Brandeis and interacted with post-docs, graduate students, pre college teachers, undergrads and other 300 exhibitors. The theme of this year conference was Science, Technology & Diversity for a Sustainable Future. In addition, SACNAS combined efforts with MAES (Society for Mexican American engineers and scientists) in order to make the experience more interdisciplinary.

For the past 30 years SACNAS has been holding this conference to enforce the underrepresented minority population in science to pursue advanced degrees, careers, and positions of leadership. A Brandeis SACNAS chapter was created over a year ago, in order to provide information and give access to professional tools to all the undergrads interested in pursuing careers in science. This year, the Brandeis SACNAS chapter was recognized during the meeting as a new chapter, and 9 of our undergraduates participated in the conference; 2 of them Angel Garcia and Kerwin Vega, presented their research in the poster sessions. You can also connect with the Brandeis chapter on Facebook.

– Yaihara Fortis

Time for Worms in Circadian Biology

Almost every organism on earth, from archae to humans, exhibits circadian rhythms – periodic cycles of behavior or gene expression that repeat approximately every 24 hours. These rhythms are generated by a circadian clock – an internal time-keeping mechanism – which can be entrained and synchronized by environmental cues such as temperature or light/dark cycles. This clock may provide organisms with an adaptive advantage throughout their life, and disruption of the function of this clock can lead to severe behavioral and metabolic disorders in humans.

For more than two decades researchers have wondered whether the tiny soil-dwelling nematode worm Caenorhabditis elegans, one of the foremost model organisms, contains a circadian clock. Circadian rhythmic behaviors described previously in C. elegans are variable and hard to quantify, and no genes were known to exhibit gene expression oscillations with 24 hr cycles as shown in many other animals.

Now, in a recent study published in the open-access journal PLoS Biology, several students and postdoctoral fellows in the labs of Piali Sengupta and Michael Rosbash joined forces and took on the challenge to identify C. elegans genes under clock control.

Light and temperature cycles both drive and entrain 24 hr oscillations in gene expression in C. elegans.

They showed that indeed C. elegans contains genes whose expression cycles in a circadian manner. They found that light and temperature cycles appear to regulate different sets of genes (see above), indicating that these stimuli may entrain two distinct clocks. Moreover, the underlying clock mechanisms may not be dependent on oscillations of known clock genes. “These findings were surprising to us since Drosophila only has a single conserved clock running in multiple cells and tissues” says Alexander van der Linden – lead author and former postdoctoral fellow in the Sengupta Lab.

C. elegans has a wealth of genetic and behavioral tools. The next critical step will be to identify the mechanisms underlying the C. elegans circadian clock(s). These investigations may also provide information of how the clock evolved since nematodes and humans split about 600-1200 million years ago.

Alexander M. van der Linden is now an Assistant Professor at the University of Nevada, Reno. The work was conducted in the labs of Profs. Michael Rosbash, a member of the Howard Hughes Medical Institute and Piali Sengupta in the Department of Biology. Other authors who contributed to this work include Molecular and Cell Biology graduate students Matthew Beverly, Joseph Rodriquez and Sara Wasserman (now a postdoctoral fellow at UCLA), and Sebastian Kadener, a former postdoctoral fellow who is now an Assistant Professor at the Silberman Institute of Life Science, The Hebrew University of Jerusalem, Israel.

PhD Defense Season

It’s the season for PhD defenses…

  • Apr 20: Megan Zahniser (Biochemistry), On the structure of Benzaldehyde Dehydrogenase, a Class 3 Aldehyde Dehydrogenase from Pseudomonas putida – 2pm, Rosenstiel Penthouse
  • Apr 21: Chris Hoefler (Biochemistry/Bioorganic Chemistry). Inhibitors of IMPDH: Tools for Probing Mechanism and Function – 3:40 pm, Gerstenzang 122
  • Apr 22: Tepring Piquado (Neuroscience), Language and the aging brain – Thu 4/22/2010, 2 pm, Volen 201
  • Apr 23: Suvi Jain (Molecular and Cell Biology), Regulation of DNA Double-Strand Break Repair by the Recombination Execution Checkpoint in Saccharomyces cerevisiae – 3:30 pm, Rosenstiel 118
  • Apr 29: Ben Cuiffo (Molecular and Cell Biology), Targeting RAS palmitoylation in hematological malignancies – 2 pm, Abelson 131

Dilute-’N’-Go sequencing

Prof. Larry Wangh and his lab are interested in detecting changes in mitochondrial genomic sequences that result from aging, disease, or drugs.  To do this, they use LATE-PCR, an advanced form of asymmetric PCR, to detect mutations in the mitochondria by using multiplexes to study many mitochondrial genes at the same time.  LATE-PCR generates single DNA strands that are easily diluted for sequencing.  In the past. they have only been able to sequence one DNA strand from these multiplex reactions.

In a recent publication in Nucleic Acid Research, staff members Yanwei Jia and John Rice, along with Molecular and Cell Biology grad student Adam Osborne, describe the development of a blocking reagent that allows them to sequence both strands of the product DNA, thus allowing for the easy verification of mutations.

The figure at right shows that without a blocker (BLK), one is not able to obtain the excess (XP) strand sequence from a multiplex reaction.  Using a blocker one is able to get not only the limiting (LP) strand, but also the excess strand from the same multiplex

Post-translational modifications of Ras Oncogenes

Ras oncogenes were first discovered almost 40 years ago, when scientists experimenting with what would later be known as retroviruses found that virus taken from a leukemic rat could induce sarcomas in other rodents.  Today we know that activating mutations of human RAS are present in ~30% of all human cancers, including both solid tumors of nearly every tissue type as well as hematological malignancies.  But despite decades of study and a wealth of knowledge collected about RAS family proteins as well as their upstream activators and downstream signaling effectors, targeting oncogenic RAS has remained elusive.

Recently, much effort had been focused on developing RAS farnesyltransferase inhibitors, which target an essential post-translational modifying enzyme which adds a farnesyl-lipid necessary for membrane anchoring to RAS, which is normally tethered to the inner face of the plasma membrane.  However, these inhibitors have not been effective as hoped, as a geranylgeranyl-lipid can be alternatively added  by another enzyme when farnesyltransferase is inhibited.  Targeting both enzymes subsequently proved to be too toxic to normal cells.

A recent paper in Blood by Ben Cuiffo, a Molecular and Cell Biology graduate student, and Prof. Ruibao Ren, sets the sights on another post-translational modification: palmitoylation.  Palmitoylation serves as a second membrane anchor for some RAS isoforms, allowing them entry to the secretory pathway to traffic from the Golgi to the plasma membrane.  The necessity for palmitoylation for oncogenic transformation was previously unclear as RAS signaling scenarios from the Golgi have been characterized in a variety of cell types in culture.  Cuiffo and Ren made use of a mouse leukemia model driven by oncogenic N-RAS to drive leukemogenesis in vivo. They found that a point mutation that prevents palmitoylation but does not affect RAS activation was unable to drive leukemogenesis in this model.  The finding that palmitoylation is essential for N-RAS leukemogenesis in vivo exposes a potentially powerful new cancer target, not only for N-RAS driven leukemias, but for a variety of malignancies that rely on N-RAS to transduce oncogenic signals.

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