Timo received his undergraduate degree in Physics from UC  Berkeley and his PhD in Biophysics from Johns Hopkins. For the past few years he has been carrying out postdoctoral research at UCSF in the lab of David Agard.  He works at the nexus of structural biology and the physical chemistry of protein folding, focusing on a perplexing, challenging class of “molecular chaperones,” proteins that help other proteins fold properly into their native conformations.  One of the great puzzles in this biologically crucial field is how these chaperones recognize and engage with the proteins emerging from the ribosome that are improperly folded and need their energy-dependent attention.  Moreover, this process is intimately related to the unfolded protein response, a kind of cellular panic-button.  To attack these kinds of questions, Timo applies a wide range of structural and kinetics methods and in his postdoctoral work has shown how these may be cleverly integrated to picture the mechanisms of highly dynamic chaperone proteins. He is beginning new projects to develop sensors that will allow him to dissect the actions of chaperones in live cells, to complement the mechanistic pictures emerging from his in vitro studies in purified, defined systems.

In many viral families, a protein shell called a capsid forms around the viral genome during the assembly process. Capsids can also assemble around nucleic acids in solution, indicating that a host cell is not required for their formation. Since capsid proteins are positively charged, and nucleic acids are negatively charged, electrostatic interactions between the two are thought to be important in capsid assembly. Current questions of interest are how structural features of the viral genome affect assembly, and why the negative charge on viral genomes is actually far greater than the positive charge on capsids. These questions are difficult to address experimentally because most of the intermediates that form during virus assembly are too short-lived to be imaged.

Snapshots from a computer simulation in which model capsid subunits (blue) assemble around a linear, negatively charged polymer (red). Positive charges on the capsid proteins are shown in yellow.

In a new paper in eLife, Brandeis postdoc Jason Perlmutter, Physics grad student Cong Qiao, and Associate Professor Michael Hagan have used state of the art computational methods and advances in graphical processing units (on our High Performance Computing cluster) to produce the most realistic model of capsid assembly to date. They showed that the stability of the complex formed between the nucleic acid and the capsid depends on the length of the viral genome. Yield was highest for genomes within a certain range of lengths, and capsids that assembled around longer or shorter genomes tended to be malformed.

Perlmutter et al. also explored how structural features of the virus — including base-pairing between viral nucleic acids, and the size and charge of the capsid — determine the optimal length of the viral genome. When they included structural data from real viruses in their simulations and predicted the optimal lengths for the viral genome, the results were very similar to those seen in existing viruses. This indicates that the structure of the viral genome has been optimized to promote packaging into capsids. Understanding this relationship between structure and packaging will make it easier to develop antiviral agents that thwart or misdirect virus assembly, and could aid the redesign of viruses for use in gene therapy and drug delivery.

Perlmutter JD, Qiao C, Hagan MF. Viral genome structures are optimal for capsid assembly. eLife 2013;2:e00632

• story at Brandeis NOW
• new paper from Molecular Biology of the Cell on the Formation of membrane ridges and scallops by the F-BAR protein Nervous Wreck.

In a recently published study in PNAS (1), biophysicists Larry Friedman and Jeffrey Mumm worked with Prof. Jeff Gelles in the Brandeis Biochemistry department to test key predictions of the FD model.  They used a novel light microscope that Friedman and colleagues invented and built at Brandeis, a microscope that can directly observe the binding of an individual RNA polymerase to a single DNA.  The scientists studied the σ⁵⁴ RNA polymerase holoenzyme, an RNA polymerase found in most species of bacteria.  Surprisingly, none of the three predictions of the FD model that the experiments tested were found to be valid, demonstrating that target finding by the polymerase is not accelerated by sliding along DNA.  Friedman and colleagues instead propose that RNA polymerases are present in such large numbers that they can diffuse through the cell and efficiently bind to their target sites directly.  The absence of FD may explain how other proteins can bind to positions on the DNA that flank gene start sites and yet not interfere with RNA polymerase finding the gene.

Is this the end of the story? Not likely, given previous publications suggesting FD plays a role for some other DNA binding proteins. Using single-molecule techniques like those developed in the Gelles lab, scientists in next few years should give us a better idea if FD is very rare or very common. [editor: as a chemical engineer, I'm sad to see FD not have a role -- it seemed like such a nice theory...]

Friedman LJ, Mumm JP, Gelles J. RNA polymerase approaches its promoter without long-range sliding along DNA.  Proc Natl Acad Sci U S A. 2013 May 29. [Epub ahead of print]

Marder is Victor and Gwendolyn Beinfield Professor of Neuroscience at Brandeis and Head of the Division of Science, as well as past president of the Society for Neuroscience. The Gruber Prize, awarded annually, includes a cash award of $500,000. The award ceremony will take place at the Society for Neuroscience meeting in November, 2013.

• story at BrandeisNOW

D-Day for summer seminars this year is June 6, when the Biochemistry & Biophysics Summer Pizza Talks series kicks off with Dr Markus Grütter of the University of Zurich. Grütter will give a special summer on his recent breakthrough-structure of the first heterodimeric ABC transporter. This structure is important because the ABC transporter is a homologue of the CFTR channel (disrupted in cystic fibrosis, one of the most common human genetic diseases). The talk will be in Gerstenzang 121 at Noon on Thursday, June 6.

The Life Sciences Summer Research Seminar Series will start on Monday, June 24, with a talk by distinguished alumna Leslie Meltzer ’03, who has returned to the Boston area as Associate Director of U.S. Medical Affairs at Biogen IDEC, having paid a visit to the other coast to get a Ph.D. in Neuroscience at Stanford in 2008, working with Karl Deisseroth. The Life Sciences Summer Research Seminar Series is organized by the Brandeis University Postdoctoral Association and will be held on Mondays at noon in Gerstenzang 121.

Join us THIS Monday, June 3, at 6:00pm at the Elephant Walk in Waltham for our next Brandeis Café Science! Professor of Physics Bulbul Chakraborty will take you on a journey through the world of granular matter: matter made out of large objects for which gravity is important and temperature is not.  This is stuff that we see around all around us but know very little about.

For the last five years Prof. Chakraborty has been working on developing a theory of granular materials that can predict their collective behavior. How do sand grains assemble into sand dunes and what causes them to avalanche?  Her research has led to a new paradigm for the emergence of solid-like properties.  Prof. Chakraborty will take you along on her journey to the discovery of this new paradigm as she asks you the questions that she asked herself.

The lateral hypothalamus (LH) is a region of the brain important for feeding. In a rodent, damage the LH, and the rodent may starve itself to death; stimulate it, and you get a curious mix of voracious eating and expressions of disgust over what is being eaten. Such data suggest that LH plays a complex game of balancing escape and avoidance, palatability and aversion, during the evaluation of a taste stimulus. Little is known, however, about how neurons in LH actually respond to tastes of different valences.

Brandeis postdocs Jennifer Li and Takashi Yoshida. undergraduate Kevin Monk ’13, and Associate Professor of Psychology Don Katz have recently published a study of neuronal reponses in LH in the Journal of Neuroscience. They have shown that taste-responsive neurons in LH break neatly down into two groups–one that responds preferentially to palatable tastes and one to aversive tastes. Virtually every taste neuron in LH could be identified as a palatable- or aversive-preferring neuron. In addition, even without considering the specific tastes to which a particular neuron responded, these two groups of neurons could be differentiated according to their baseline firing rate, shape of response, and tuning width. While these neurons were spatially intermingled, several pieces of data (functional connectivity analysis, relationship to responses in amygdala and cortex) suggest that they are parts of distinct neural circuits. These results offer insights into the multiple feeding-related processes that LH manages, and how the hypothalamus’ role in these processes might be related to its connection to other parts of the taste system.

Li JX, Yoshida T, Monk KJ, Katz DB. Lateral Hypothalamus Contains Two Types of Palatability-Related Taste Responses with Distinct Dynamics. J Neurosci. 2013;33(22):9462-73.

The Shaw Prize, established under the auspices of Mr Run Run Shaw, honours individuals, regardless of race, nationality, gender and religious belief, who have achieved significant breakthrough in academic and scientific research or applications and whose work has resulted in a positive and profound impact on mankind. There are three annual prizes: Astronomy, Life Science and Medicine, and Mathematical Sciences, each bearing a monetary award of one million US dollars. The presentation ceremony is scheduled for Monday, 23 September 2013.

A new paper in J. Neuroscience from the Paradis lab shows that treatment of cultured neurons with the extracellular domain of the protein Sema4D causes a rapid increase (i.e. within 30 minutes) in the density of functional GABAergic synapses. Further, addition of Sema4D to neurons drives GABAergic synapse formation through a previously unappreciated mechanism: the splitting of pre-existing assemblies of the Gephyrin scaffolding protein. To our knowledge this is the fastest demonstration of synapse formation reported thus far and has significant implications for our understanding of the mechanisms of GABAergic synapse formation.

While the underlying mechanism of epileptogenesis is largely unknown, recurrent seizures emerge when there is an increase in network activity. One possible therapeutic treatment would be to restore normal network activity by increasing network inhibition. In an in vitro model of epilepsy, acute treatment with the protein Sema4D rapidly silences neuronal hyperexcitability, suggesting a possible use of Sema4D as a disease-modifying treatment for epilepsy.

Lead authors on the paper were Marissa Kuzirian, a grad student in the Neuroscience Ph.D. program, and Anna Moore, a Brandeis Neuroscience postdoctoral fellow.

• From Chris Miller‘s lab, bacterial antiporters do act as “virtual proton efflux pumps”:
  • Tsai MF, Miller C. Substrate selectivity in arginine-dependent acid resistance in enteric bacteria. Proc Natl Acad Sci U S A. 2013;110(15):5893-7.
  • Tsai MF, McCarthy P, Miller C. Substrate selectivity in glutamate-dependent acid resistance in enteric bacteria. Proc Natl Acad Sci U S A. 2013;110(15):5898-902.
• Are ninja stars responsible for controlling actin disassembly? Seems like the Goode lab might think so.
  • Chaudhry F, Breitsprecher D, Little K, Sharov G, Sokolova O, Goode BL. Srv2/cyclase-associated protein forms hexameric shurikens that directly catalyze actin filament severing by cofilin. Mol Biol Cell. 2013;24(1):31-41.
• What do you get from statistical mechanics of self-propelled particles? The Hagan and Baskaran groups team up to find out.
  • Redner GS, Hagan MF, Baskaran A. Structure and dynamics of a phase-separating active colloidal fluid. Phys Rev Lett. 2013;110(5):055701.
• From John Lisman and Ole Jensen (PhD ’98), thoughts about what the theta and gamma rhythms in the brain encode
  • Lisman JE, Jensen O. The theta-gamma neural code. Neuron. 2013;77(6):1002-16.
• From Mike Marr‘s lab, studeies using genome-wide nascent sequencing to understand how transcrption bursting is controlled in eukaryotic cells
  • Pennington KL, Marr SK, Chirn GW, Marr MT, 2nd. Holo-TFIID controls the magnitude of a transcription burst and fine-tuning of transcription. Proc Natl Acad Sci U S A. 2013;110(19):7678-83.
• From the Lau and Sengupta labs, RNAi pathways contribute to long term plasticity in worms that have gone through the Dauer stage
  • Hall SE, Chirn GW, Lau NC, Sengupta P. RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans. RNA. 2013;19(3):306-19.
• Can nanofibers selectively disrupt cancer cell types? Early results from Bing Xu‘s group.
  • Kuang Y, Xu B. Disruption of the Dynamics of Microtubules and Selective Inhibition of Glioblastoma Cells by Nanofibers of Small Hydrophobic Molecules. Angew Chem Int Ed Engl. 2013.

  

I’m entering a nationwide video/poster competition organized by the National Science Foundation (NSF) under the IGERT program.  There are over 100 three-minute-videos/posters in the competition.  The videos/posters are divided into 18 fields, all of which are multidisciplinary.  Mine covers cognition/biology/physics.

The competition has a Public Choice award.  Winning the award requires Facebook “likes” on my page.  I need on the order ~1000 “likes” to be in contention.  The bar has been raised from last year’s.  The competition is fierce.  Each/every vote from the Brandeis community counts!

The competition opens today (5/21) and ends Thursday (5/23) at 10pm.  For a vote to count, it is imperative to click on the “Public Choice” button, which would then trigger a Facebook “like” sign-in.  Anyone with an existing Facebook account can contribute.

Here’s the link to my 3-minute video/poster:

http://posterhall.org/igert2013/posters/402

Act now! Tthe competition closes on Thursday at 10pm!

Hope you enjoy the videos!

Update (2 pm):

Andrew Russell from the Petsko-Ringe lab also has a poster in the competition on studying Aβ oligomers to understand Alzheimer’s Disease – check it out — vote early, vote often?

http://posterhall.org/igert2013/posters/416

see also: http://blogs.scientificamerican.com/roots-of-unity/2013/05/15/goldbach-variations/

At Brandeis, Asher worked on his senior thesis in chemistry with Professor Milos Dolnik as part of the Epstein Group. They studied the growth dynamics of Turing patterns in photosensitive reaction-diffusion systems. As part of the 2011 NYU MRSEC Research Experiences for Undergraduates (REU) program Asher worked with Paul Chaikin to study active colloids, and they recently published an article in Science entitled “Living Crystals of Light-Activated Colloidal Surfers”. The article received attention from the press, including the LA Times, Wired, and Ars Technica.  Last summer Asher participated in the Columbia EFRC Research Program for Undergraduates (RPU) and studied silver plasmonic nanoparticles with Louis Brus.

Asher will be attending California Institute of Technology this coming fall in the field of Chemical Physics.

The panelists gave the audience a sense of what their specific careers entail, and how skills they had acquired during their PhDs were highly relevant to their current work. Some of the transferable skills mentioned included critical thinking and the ability to quickly synthesize information and distill what is most important and interesting about a given scientific finding. These skills enabled them to be highly effective in their jobs, whether efficiently evaluating scientific manuscripts as an editor, or determining the crux of a client’s research as a consultant or intellectual property lawyer.

Current jobs for recent Brandeis Life Science PhDs (Neuro, Mol Cell Biol, Biochem, Biophys graduates, 2002 and beyond, n=200)

Having completed their transition from academia to the business world, panelists were able to highlight some of key cultural and practical differences associated with working in a profit-driven industry. While Derek described his lab at Pfizer as largely mimicking an academic environment (minus the need to perpetually write grants), he and other panelists noted that, unlike academia, business evaluations are based almost exclusively on having achieved specific pre-determined goals. On the upside, for those who exceed expectations in business, there are lots of opportunities to move up the ladder. Other differences that panelists encountered in their non-academic professions included firmer deadlines, higher dressing standards, and less flexible hours.

While the majority of the discussion was specific to the panelists’ career paths, much of the advice applied to career searches in general. The importance of good networking was emphasized. Job seekers were encouraged to make the most of their networks – and their network’s network as well. Each panelist explained how he or she had acquired their job through a combination of effective networking, being proactive, and in some cases, luck. Panelists were quick to point out, though, that time and effort invested were positively correlated with “luck.”

Panelists stressed that effective networking required quickly following through with contacts, and being prepared to impress key contacts with excellent questions that demonstrate your research on a given company. They encouraged the audience to be proactive, and if needed persistent, in reaching out to people whose work they find interesting. Several panelists also emphasized the benefits of acquiring job-related experience. They noted this was a good way to both boost your resume and get a better sense of whether a given profession is the right fit for you. For example, John Garvey recommended joining a consulting or biotech club, and/or taking a business class. Getting involved in job-related activities is also excellent ways to establish good contacts for networking.

Overall the panelist presented several attractive alternatives to a traditional academic career. By carefully analyzing his or her personality, strengths, and working style, each of them had found a rewarding career that effectively utilized their scientific background/training. Priya, the editor, described how she enjoyed being able to see where scientific fields are going and staying up to date with the latest scientific breakthroughs. Derek, the pharmaceutical researcher, explained how it was gratifying for him to be working directly to develop drugs that could benefit people. John, the lawyer, explained how his work solving business problems was important because it helped provide pharmaceutical companies with the financial resources to bring new life-saving drugs to market. The general take-home message from all of the panelists was that, using the right career strategies, one can effectively use one’s PhD as a launching point to successfully pursue many different avenues outside of academia. Those interested in getting a better sense of what career might be a good fit for them are encouraged to visit http://myidp.sciencecareers.org and fill out the survey.

What do Brandeis life science PhD students go on to do?

For more information, see the story at Brandeis NOW or the Turrigiano lab website.

Please visit the Brandeis-India Science Scholars website for additional information and to access the application. Additional funding opportunities are available for this program through the Brandeis-India Initiative and the Physics Department.  More information about these opportunities is available in the financial section on the program website.

Application deadline: May 10th, 2013

Please feel free to contact Amber Thacher in the Office of Study Abroad with any questions about the program or application process.  athacher @t brandeis dot edu