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.

Lots of seminars coming

Whole bunch of seminars and award lectures coming up in the next week. Steven Reppert from U. Mass. talks today at 4 about monarch butterfly migration and its relationship to the circadian clock. On Monday at noon, Giovanni Bosco (PhD in Mol Cell Biol, Brandeis, 1998) will talk about condensins and global chromosome structure.

On Tuesday, we have the 39th Annual Rosenstiel Award lectures at 4. Jules Hoffman and Ruslan Medzhitov will get award “for their elucidation of the mechanisms of innate immunity”.

Next Wednesday we have the Heart Research Series lecture. Monty Krieger, Whitehead Professor of Molecular Genetics at MIT, will talk about cholesterol, genetics, and heart disease. Finally, next Thursday will have Josh Tenenbaum from MIT speaking in the Psychology Colloquium about “How to Grow a Mind”.

Details (time, room number) about upcoming seminars are always available in the Seminars widget in the left-hand column on this blog.

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