Yeast genetics and familial ALS

In a recent paper in PLoS Biology, “A Yeast Model of FUS/TLS-Dependent Cytotoxicity“, Brandeis postdoc Shulin Ju and coworkers applied yeast genetics to examine the function of the human protein FUS/TLS. The gene for FUS/TLS is mutated in 5-10$ of cases of Familial ALS. The yeast model expressing the mutant protein recapitulates many important features of the pathology.

A particular feature of interest is that  FUS/TLS form cytoplasmic inclusions of this protein which is normally localized to the nucleus. Over-expression of a number of yeast proteins rescues the cells from the toxic effect without removing the inclusions. The results are suggested to implicate RNA processing or RNA quality control in the mechanism of toxicity, which I find really interesting in light of the talk Susan Lindquist (an author on this paper) gave at Brandeis about yeast prions and regulatory proteins earlier this month.

Other authors on the paper include Brandeis professors Dagmar Ringe and Gregory Petsko, and Brandeis alumni Dan Tardiff (PhD, Mol. Cell. Biol.,  ’07), currently a postdoc in the Lindquist lab at the Whitehead Institute,  and Daryl Bosco (PhD, Bioorganic Chem, ’03), currently on the faculty at U. Mass. Medical School.

For more information, please see the paper itself or the longer article about the research on Brandeis NOW.

Signals on the move

A hallmark feature of eukaryotic cells is their intricate subcellular membrane compartmentalization, which biochemically and spatially isolates cellular processes including signal transduction, protein synthesis, and energy production. Membrane-spanning proteins such as growth factor receptors are transported through these compartments by the actions of a host of membrane binding proteins that bend, pinch and move bits of cargo-containing membrane from one compartment to another. Growth factor receptors change their signaling properties as they transit through these different compartments, and so cells can turn growth factor signaling up or down by regulating the rate of transit. The challenge is to understand how networks of hundreds of interacting membrane deforming proteins work to control cargo traffic, and how these proteins might themselves be regulated by the cell to reroute cargo.

Live imaging of dynamic interactions between subcellular compartments in fly neurons.
(click to watch movie)

Now, in a recent study published in the Journal of Cell Biology, new Biology faculty member Avital Rodal, together with Troy Littleton at MIT, identify a novel interaction between two membrane-binding proteins, Nervous Wreck (Nwk) and Sorting Nexin 16 (SNX16), that are critical for controlling the traffic of growth factor receptors that drive the expansion of neuronal arbors. Using the neurons that innervate muscles in fruit fly larvae as a model, Rodal and colleagues show that a physical association between these two proteins is necessary to turn off signaling by receptors that have been previously activated by growth factors. Perplexingly, though Nwk and SNX16 must physically interact to execute their role in driving membrane movements, they appear to reside in different subcellular compartments, in different locations within the neuron. To solve this conundrum, Rodal and colleagues took advantage of the spinning disk confocal microscope in the Brandeis Correlative Light and Electron Microscopy facility to look at the dynamic behavior of these compartments in living neurons in larvae. They found that the two distinct compartments inhabited by Nwk and SNX16 undergo dynamic and transient interactions, which represent the point in space and time that signaling receptor cargo is transferred between compartments. These receptor trafficking events are implicated in diseases ranging from neurodegenerative disease to mental retardation and addiction, underlining the health importance of understanding how signal transduction is modulated by intracellular membrane traffic in neurons.

Strom receives 2011 Verna Regan Award

Michael Strom, a year 5 PhD student, is the recipient of the 2011 Verna Regan Award for the Outstanding Teaching Fellow in Psychology.

The award is given annually to the PhD student who was unusually helpful to professors in carrying out his or her duties as a teaching fellow, who has demonstrated exceptional abilities to communicate information and to teach undergraduate students, and who showed a high level of responsiveness in addressing the needs of those students.

Mike, who was selected from a field of other qualified and worthy candidates, will be among twenty-two outstanding teaching fellows to be honored at a reception to be held by the Graduate School of Arts and Sciences on Friday, May 6th, where he will be presented with a certificate and honorarium.

Graduate Student Andreas Rauch awarded Outstanding Teaching Fellow in Physics

Graduate student Andreas Rauch has been awarded the Outstanding Teaching Fellow award in Physics based on his overall teaching excellence, student and course instructor evaluations, and letters from faculty.  According to Professor John Wardle, Chair of the Physics Department, “Andreas’ several years of teaching math in German schools has helped make him one of the best and most experienced Teaching Fellows I have known. This award is very well deserved.”  Andreas has been a teaching fellow in Physics 29a, Electronics Laboratory with Professor Larry Kirsch; Physics 25b, Astrophysics with Professor John Wardle; Physics 19b, Physics Laboratory II with Professor Zvonimir Dogic; and Physics 31a, Quantum Theory I with Professor Matthew Headrick.

Four other teaching fellows in the sciences will also be recognized at this year’s TF Award reception on May 6:

Mark Bezpalko (Chemistry)
Ryan Broderick (Mathematics)
Xiaochuan Cai (Chemistry)
Fan Zhao (Chemistry)

Biochemistry Senior Research Talks on April 29

The Department of Biochemistry presents senior research talks by the 2010/2011 Biochemistry Honor and BS/MS Candidates on Friday, April 29, 11:30-1:30pm in Gerstenzang 121.

Benjamin D. Hornstein – BS/MS
Seq A: construction and analysis of mutants
Advisor: Sue Lovett

Marcus R. Kelly– BS/MS
Replacement Matrices for Transmembrane Proteins
Advisor: Douglas Theobald

Yuliya Y. Mints – BS/MS
Inosine Monophosphate Dehydrogenase and Transcription: a mechanism for retinitis pigmentosa?
Advisor: Liz Hedstrom

Sarah Naomi Olsen – BS/MS
Isolation, Purification, and Characterization of (+)-4R-limonene synthase
Advisor: Dan Oprian

Benjamin M. Whitlock – BS/MS
PABPN1 and SKIIP: A putative mechanism for the onset of Oculopharyngeal Muscular Dystrophy
Advisor: Dagmar Ringe

Philip D. Lessans – BS
Developing a Method of Extracting Native U snRNPs from eukaryotic cells using Snurportin 1 constructs
Advisor: Daniel Pomeranz Krummel

Jessica P. Liken – BS
Deletion Library Screen for Enhancers and Suppressors of ALS-associated FUS/TLS Toxicity in Yeast
Advisor: Greg Petsko

Everyone is welcome and encouraged to come. Pizza will be provided.

MRSEC summer course in Microfluidics (June 27- July 1, 2011)

Microfluidics is a recently introduced field of research area in which scientists study the behavior, precise control, and manipulation of fluids that are geometrically constrained to a small, typically sub-millimeter scale, where the dominant phenomena include diffusion, laminar flow, surface tension, and evaporation.  By incorporating these new tools, researchers are able to create novel functions and methods. Emerging application areas for this technology include micro total analysis system (μTAS), tissue engineering, and drug screening. One of the major benefits of this technology is its ability to make an economical device that requires very small sample and small quantities of expensive reagent.  It may also be possible to integrate more components in a device at higher resolution with this technology.

The Brandeis Materials Science Research and Enginering Center offers a one-week summer course from June 27 – July 1, 2011, “Introduction to Microfludics Technology“. The course will introduce students to the microfabrication technologies available to build microfluidic devices. This course has been created in response to the great interest from industry, government and academia in the field of microfluidics. We will build several microfluidic devices to understand the microscale phenomena and their applications. Throughout the course, we will place an emphasis on hands-on experimentation with microfluidic systems where laminar flow, surface tension, and molecular diffusion dominate.

Students having fun in the cleanroom

The instructor, Dr. Dongshin Kim, received his Ph.D. (2006) degree in Mechanical Engineering, MS degrees in both Biomedical (2004) and Mechanical (2001) Engineering from the University of Wisconsin-Madison. After his Ph.D. program, Dr. Kim received biological training on tissue engineering in the Department of Animal Sciences at the University of Illinois as a postdoctoral associate in 2006. In January of 2009, Dr. Kim joined the Materials Research Science and Engineering Center (MRSEC) at Brandeis University. Since then, Dr. Kim has been collaborating with many faculty members and scientists in the field of life science to implement the microfluidics technology into their researches.

Two more NSF GRFP fellowship winners

Brandeis had 1 current undergraduate, 7 undergraduate alunmi, and 1 incoming graduate student win NSF graduate research fellowships this year. In addition to those cited below, Richard Stefan Isaac ’10 and Orly Wapinski ’09 were also selected. Isaac graduated magna cum laude with a BS/MS degree with high honors in Biochemistry. His thesis work “Functional Characterization of Regulators of Bacterial Pathogenicity and
Metabolism
” was done in the Petsko/Ringe lab. His work teaching in the Biology laboratory also resulted in a paper  in CBE Life Science Education. Isaac is currently a graduate student at Univ. of California, San Francisco. Wapinsky received a BS degree with Highest Honors in Biology, doing in her thesis work “Characterization of Interferon Regulatory Factor-4 mutants” with Professor Ruibao Ren. Wapinski is currently studying at Stanford.

Daniel Graham ’10, and Aaron Gell ’10, and Jeffrey Dobereiner ’09 awarded 2011 NSF Graduate Research Fellowships

Former chemistry majors Daniel Graham ’10, Aaron Gell ’10, and Jeffrey Dobereiner ’09 have been awarded National Science Foundation Graduate Research Fellowships. These Fellowships, geared towards ensuring the vitality of the country’s scientific workforce, support the graduate education of individuals who have demonstrated their potential for significant achievements in scientific research.  Dan and Aaron are currently first year graduate students at MIT, pursuing Ph.D.s in inorganic chemistry.  Dan received highest honors in chemistry for thesis research conducted in the lab of Professor Christine M. Thomas, and is currently continuing to investigate chemical approaches to renewable energy strategies in the lab of Professor Daniel Nocera at MIT.  Aaron, also an inorganic chemist, conducted undergraduate research in the Brandeis chemistry department under the supervision of Professor Bruce Foxman. Jeff was a double major in anthropology and chemistry at Brandeis and is currently pursuing a Ph.D. in Archaeology at Harvard University, where he is applying his chemistry knowledge to the analysis of ancient artifacts. In addition, Delora Gaskins, a 2011 incoming graduate student in the area of physical chemistry, was awarded an NSF Fellowship.  Delora is completing her undergraduate degree at Cal. State. – Long Beach and hopes to join the lab of Professor Irving Epstein in the fall of 2011.

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