Andy Berglund (PhD ’97) to talk about Myotonic Dystrophy

Professor Andy Berglund from the Institute of Molecular Biology at U. Oregon will be on campus on Wednesday, Jan. 19 to talk about Understanding Protein-RNA Interactions in Myotonic Dystrophy and a Small Molecule Approach to Target the Toxic Element in this Disease at the year’s Kaplan Lecture in the Joint Biology/Biochemistry Semester Series. Berglund received his Ph.D. in Biochemistry from Brandeis in 1997, working on RNA processing, yeast splicing more specifically, in Michael Rosbash’s lab. He did a seminal piece of work for his thesis, which showed that the yeast branchpoint binding protein BBP, also known as SF1 in mammals, recognizes the yeast branchpoint sequence UACUAAC. After doing postdocs with Steve Schultz and Tom Cech at U. Colorado, Berglund assumed a faculty position at U. Oregon in 2002, where he is now an Associate Professor. His current research aims in part to understand and develop therapies for a specific form of human muscular dystrophy, which is called myotonic dystrophy. This disease is caused by expression of a toxic RNA,  which interacts with the RNA binding protein muscleblind and thereby indirectly interferes with RNA splicing. So Berglund has continued his interest in splicing, but with this more human disease focus. Indeed, his lab has identified small molecules that could potentially be used to counter these splicing defects .

The Kaplan Lecture is held annually to honor the memory of Nate Kaplan, who was the first chair of the Graduate Department of Biochemistry at Brandeis, playing a huge role in the emergence of Brandeis as a major research university. Kaplan lecturers are members of the Brandeis Biochemistry community who have gone on to distinguished research careers elsewhere. The talk will take place in Gerstenzang 121 at 4:00 pm, Brandeis community members are invited to attend.

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.

BIOL 99 AND NEUR 99 Senior Honors Talks

Senior honors presentations and defenses for Biology and Neuroscience are this week and next Monday.

Name      Faculty Sponsor & Committee  Time & Location of Talk

Biol 99

Alicia Bach Dagmar Ringe, Neil Simister, Liz Hedstrom May 10   3 pm    Bassine 251
Kristin Little Bruce Goode, Joan Press, Satoshi Yoshida May 6    10 am    Bassine 251
Spencer Rittner KC Hayes, Carolyn Cohen, Larry Wangh May 6    3 pm      Bassine 251
Danielle Saly Michael Rosbash, Mike Marr, Nelson Lau May 10   11 am   Bassine 251
Sue Yen Tay Jim Haber, Sue Lovett, Joan Press  May 7    11am     Bassine 251
Alan Tso Daniela Nicastro, Liz Hedstrom, Greg Petsko May 10   2 pm    Bassine 251
Hannah Worchel Jim Morris, Ruibao Ren, Paul Garrity   May 6    2 pm     Bassine 251

Neur 99
Sarah Pease Sue Paradis, Gina Turrigiano, Paul Miller  May 10   11 am   Volen 201
Solon Schur John Lisman, Eve Marder, Paul Miller May 6    10 am   Volen 201
Alexander Trott Leslie Griffith, Piali Sengupa, Melissa Kosinski-Collins May 6    11 am   Volen 201
Dylan Wolman Sue Paradis, Sacha Nelson, Piali Sengupta May 10   1 pm    Volen 201

Faculty research mentor (emphasized) is chair of the committee.

Back online

We’ve been off-line for a while, and now we’ve moved into the new version of WordPress supported by the campus IT folks. It should now be relatively easy for labs to post themselves to this blogs.

What have we missed? Well, for one, Michael Rosbash and Jeff Hall are getting the Gruber Neuroscience Prize, together with Michael Young (Rockefeller U), for their work on genetics of circadian rhythms.

I’ll post some more of the “backdated” news when I get a chance. Feel free to ask for an account so you can do it yourself…

Drosha and Pasha

No, this isn’t a Russian short story.

Lead authors postdoc alum Sebastian Kadener and Mol Cell Biol graduate student Joe Rodriguez and their coworkers used tiling arrays to look for targets of the enzyme Drosha in “Genome-wide identification of targets of the drosha–pasha/DGCR8 complex”, a paper recently published in the journal RNA. Drosha is a type III RNAse that is involved in the processing of  miRNAs. This paper demonstrates for first time that this enzyme is not only involved in miRNA processing, but can also process mRNAs.  Interestingly, the best example of an mRNA processed by Drosha is the mRNA that encodes another miRNA processing enzyme, the protein Pasha. As this is a partner of Drosha (the two proteins work together), the findings suggest that  there is a feedback loop that controls the abundance of the miRNA processing machinery and probably the abundance of miRNAs themselves.

Rise and shine, little fly

Most animals sleep, but why they sleep and how the brain generates sleep is mysterious. In a recent study published in Neuron, postdoc Katherine Parisky and colleagues use genetic tools to manipulate the activity of neurons that control sleep in flies. Their results demonstrate that in the fly sleep is generated by GABAergic inhibition of a small cluster of peptidergic neurons within the circadian clock. Flies carrying mutations in this peptide, PDF, or its receptor, are hypersomnolent, similar to human narcoleptics who have defective signaling by the peptide hypocretin/orexin. These results suggest that the circuit architecture used to control arousal is ancient.

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