Another way that flies sense temperature

If you remember your (bio-)physical chemistry, you’ll remember that most proteins are temperature sensitive. But which ones acts as the sensors that drive behavior in higher organisms? The Garrity Lab at Brandeis has been working on thermosensation in Drosophila, and previous work has implicated the channel protein TRPA1 as a key mediator of temperature preference and thermotaxis,  In a new paper in Nature, members of the Garrity lab working in collaboration with the Griffith and Theobald have have identified another protein, GR28B(D), a member of the family of gustatory receptor proteins, as another behaviorally important temperature sensor, involved in rapid avoidance of high temperatures. Authors on the paper include postdocs Lina Ni (lead author) and Peter Bronk, grad students April Lowell (Mol. Cell Biology) and Vincent Panzano (PhD ’13, Neuroscience), undergraduate Juliette Flam ’12, and technician Elaine Chang ’08.

  • Ni L, Bronk P, Chang EC, Lowell AM, Flam JO, Panzano VC, Theobald DL, Griffith LC, Garrity PA. A gustatory receptor paralogue controls rapid warmth avoidance in Drosophila. Nature. 2013.
  • story at BrandeisNOW


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.

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.

Detecting Mutations the Easy Way

Recent Brandeis Ph.D graduate, Tracey Seier (Molecular and Cell Biology Program), Professor Sue Lovett, Research Assistant Vincent Sutera, together with former Brandeis undergraduates Noor Toha, Dana Padgett and Gal Zilberberg have developed a set of bacterial strains that can be used as “mutational reporters”.  Students in the Fall 2009 BIOL155a, Project Laboratory in Genetics and Genomics, course also assisted in the development of this resource. This work has recently been published in the journal Genetics.

These Escherichia coli strains carry mutations in the lacZ (β-galactosidase) gene that regain the ability to metabolize lactose by one, and only one, specific type of mutation. This set allows environmental compounds to be screened for effects on a broad set of potential mutations, establishing mutagen status and the mutational specificity in one easy step.

This strain set is improved over previous ones in the inclusion of reporters that are specific for certain types of mutations associated with mutational hotspots in gene. Mutations at these sites occur much more frequently than average and involve DNA strand misalignments at repeated DNA sequences rather than DNA polymerase errors. Such mutations are associated with human diseases, including cancer progression, and have been under-investigated because of the lack of specific assays. Using this strain set, Seier et al. also identified a mutagen, hydroxyurea, used in the treatment of leukemia and sickle cell disease, which affects only the “hotspot” class of mutations. This strain set, which will be deposited in the E. coli Genetic Stock Center,  will facilitate the screening of potential mutagens, environmental conditions or genetic loci for effects on a wide spectrum of mutational events.



Left: E. coli colonies showing lacZ mutant revertants (blue pimples) arising on a white colony on growth medium containing the beta-galactosidase indicator dye,  X-gal


Phosphatases and DNA double strand break repair

When cells suffer DNA damage – as little as a single break in one chromosome – they respond by activating the DNA damage checkpoint, which prevents cells from entering mitosis until there is enough time to to repair the damage.  The principal biochemical events in the checkpoint pathway are the phosphorylations of protein kinases by other protein kinases and eventually the phosphorylation of other proteins that regulate mitosis.    When repair is complete, the checkpoint must be turned off.  Not surprisingly, the enzymes that turn off the checkpoint are phosphatases that can remove the phosphates added by the protein kinases.

The Haber lab has previously shown that, in budding yeast, a pair of PP2C phosphatases known as Ptc2 and Ptc3 were important in turning off a key protein kinase, Rad53.  A member of another phosphatase subgroup, the PP4 phosphatase Pph3, dephosphorylates a target of the checkpoint kinases, histone protein H2A.  There is one aspect that they didn’t understand at all: It seems that the intensity of the checkpoint signals must grow the longer it takes to repair DNA damage, because deletions of ptc2 and ptc3 or a deletion of pph3 prevented cells from turning off the damage signal when it took a long time – 6 hours – to repair the damage, but they had much less effect on different repair events that could complete in 3-4 hours or in less than 2 hours.  So they decided to see what would happen if they created a yeast strain lacking all three phosphatases (ptc2 ptc3 pph3), leading to a paper appearing this month in the journal Molecular and Cell Biology.

To their surprise, these cells had a new defect: they couldn’t complete the repair event itself, rather than simply being defective in resuming mitosis after repair was completed.  The mutants could not properly initiate the small amounts of DNA copying that are required for repair.  Again, the severity of the defect depends on the length of the delay it takes to initiate the repair event itself.  The figure (right) shows that the triple mutant is also much more sensitive to DNA damaging agents such as the anti-cancer drug camptothecin (CPT) and to methylmethansulfonate (MMS). These data show a complex connection between DNA damage signaling and the repair process itself, and reveal new roles for the phosphatases in DNA repair.  The work was carried out primarily by graduate student Jung-Ae Kim, now a postdoc at Rockefeller University, with help by another grad student, Wade Hicks, and by an undergraduate Sue Yen Tay, and postdoc Jin Li. The work was supported by a research and a graduate student training grant from the NIH.

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