Celebrating Chris Miller at Christravaganza Millerpalooza

Since its founding at Brandeis in 1976, Chris Miller’s lab has been home to 25 graduate students and 35 postdocs. Many of them, together with friends and colleagues from around the world, came together on July 8 and 9 for a two day symposium celebrating Chris’ 70th birthday.

For four decades Miller has used electrophysiological methods to study single ion channels. Ion channels are proteins that open and close, selectively allowing specific ions to cross cell membranes, for example to drive muscle contraction or nerve cell signaling. The selective transport of ions across membranes is a fundamental feature of cells.

Miller began studying channels selective for potassium ions, and then in 1978 discovered a chloride selective channel, from Torpedo, the first member of the important CLC chloride channels whose malfunction is implicated in a variety of diseases. (Its name comes from the electric ray Torpedo californica from which the channel was first isolated.) Chris discovered the unusual “double barreled” architecture of the CLC family of ion channels. The lab continues to work on related proteins, including Cl/H+ exchange-transporters.

Miller’s lab has followed clues in recent years to find additional novel channels to study, including bacterial proteins involved in acid resistance and most recently channels that are selective for fluoride. Chris has been a Howard Hughes Medical Institute investigator since 1989 and in 2007 he was elected to the US National Academy of Sciences.

Rod MacKinnon ’78 was Chris’ very first student while he was an undergraduate at Brandeis. After medical school, Rod came back to Chris’ lab as a postdoc, and together they investigated the mechanism of calcium activated potassium ion channels. Later, at Rockefeller University, Rod used high resolution x-ray diffraction to determine the complete molecular structure of the proteins that form the channel. For this he was awarded the Nobel Prize for Chemistry in 2003. The structure confirmed a cartoon picture of how the potassium channel works that Chris, with postdoctoral fellows MacKinnon and Jaques Neyton, had developed ten years earlier.

Chris’ wife, Brandeis Professor of Russian and Comparative Literature Robin Feuer Miller, and their three daughters were in attendance. Lulu Miller (who is also co-host of the NPR program Invisibilia) introduced her father for the final talk of the symposium.

The editors thank Dan Oprian for help with this article. The photographs were taken by Heratch Ekmekjian.

Sprout Award Winners Announced

The recipients of the 6th annual Sprout Awards have been announced. There will be eight teams from labs in the Biology, Biochemistry, and Chemistry departments sharing the $100,000 in funding in FY 2017. The Sprout program’s grant pool was doubled this year in order to expand the support for the promising innovation and research that is happening here at Brandeis University.  The Sprout program, created 6 years with the intent to encourage entrepreneurial activity, is sponsored by the Office of the Provost and the Hassenfeld Family Innovation Center. It is administered by the university’s Office of Technology Licensing

(read more at Brandeis Now).

 

Four Brandeis Science Grads Receive 2016 NSF Graduate Fellowships

GRFP_logoA science education at Brandeis University can be a springboard to future science achievements. We would like to congratulate four of our science graduates who have received the prestigious National Science Foundation Graduate Research Fellowships for 2016.

Noam Saper

Noam was an outstanding student graduating summa cum laude with highest honors in Chemistry in 2015. At Brandeis, Noam worked in the labs of Prof. Barry Snider and Prof. Christine Thomas. He co-authored 3 publications with Snider and Thomas.

Noam received multiple awards including the Barry M. Goldwater Scholarship (2014); the Elihu A. Silver Prize (2014); and the Doris Brewer Cohen Endowment Award (2015).

Following graduation and enthralled by the mysteries of the west coast, he decided to attend the University of California, Berkeley. Noam is working on mechanistic studies of Ni-catalyzed diaryl ether hydrogenolysis in Professor John Hartwig’s laboratory.

Alexandra Sun

Another outstanding Chemistry student, Alexandra Sun graduated magna cum laude with highest honors in 2015. Alexandra also worked in Christine Thomas’ lab where she carried out research on Transition Metal Complexes Featuring a Redox-Active Bidentate Amido-Phosphido Ligand. Alexandra received the Melvin M. Snider Prize in Chemistry in 2015.

She is currently a first-year student in the Chemistry Department at the University of Michigan working with Professor Corey Stephenson on developing new methods in photoredox catalysis.

Abigail Zadina

Abigail received her BS/MS in Neuroscience in 2013. Working in Michael Rosbash’s lab, she was a co-author on 2 publications and received numerous awards including the Doris Brewer Cohen award and the Elihu Silver Prize. In 2013, Abigail discussed her science experience in the Brandeis publication Imprint.

Following graduation, Abigail worked at Columbia in Richard Axel’s lab. She is currently a PhD student in Neurobiology and Behavior at Columbia University.

Joseph Jacobowitz

Joseph Jacobowitz received his BS/MS in 2014, graduating summa cum laude with Highest Honors in Biochemistry. While a Brandeis undergraduate, Joseph co-authored a publication with his faculty mentor, Doug Theobald. In 2013, Joseph received the Division of Science Prize for Outstanding Research Accomplishment and the William P. Jencks  Award in Biochemistry in 2014.

Joseph is in the Biology PhD program at MIT, working for Jing-Ke Weng on the origins of chemodiversity in plants.

Summer Research at Brandeis

All four science graduates had the opportunity to jump start their careers by doing summer research at Brandeis. Noam, Alexandra and Joseph were Division of Science Summer Undergraduate Research Fellows (SURF). Abigail received a Computational Neuroscience Traineeship.

These undergraduate research programs enable students to spend their summers at Brandeis engaged in intensive undergraduate training and summer research. Both programs provide a stipend, faculty mentoring and full-time lab research. The Summer Undergraduate Research Fellows work culminates in a poster presentation summarizing their work. The SURF program is funded by generous donations from alumni. The Computational Neuroscience Traineeship program begins in the summer and runs through the following academic year. It is funded through a grant from the National Institute on Drug Abuse. 

SPROUT Continues Growing Support for Brandeisian Innovators

Lil_Sprout_smallProgram Will Bestow Up to $100,000 to Promising Research Proposals

Could your research impact the world or do you have an idea that could create positive change? Need funding? SPROUT can help with that.

The popular SPROUT program, now in its sixth year, has announced increased funding for the 2016 round of proposals. SPROUT is funded by the Office of the Provost and run by Office of Technology Licensing. This year the Hassenfeld Family Innovation Center, recently created to support entrepreneurial and innovative collaborations happening across campus, contributed an additional $50,000 to be disbursed among the most promising requests.

Historically, the program has supported a diverse scope of lab-based innovations from all departments in the sciences  including Biology, Biochemistry, Physics, and Chemistry.  Past candidates have proposed projects ranging  from early‐stage research and development to patent‐ready projects ranging from treatments for diseases to lab tools.  Brandeis lab scientists have pitched their projects, including HIV vaccines (Sebastian Temme, Krauss lab),  neuroslicers (Yasmin Escobedo Lozoya, Nelson lab) and the use of carrot fiber as an anti-diabetic  (Michelle Landstrom, Hayes lab) to a panel of distinguished, outside judges. A SPROUT award can jumpstart your innovation and lead to continued opportunities. SPROUT awardees researching the use of carrot fiber as an anti-diabetic food agent were just awarded additional funding by the Massachusetts Innovation Commercialization Seed Fund program.

Other successful projects include “Enzymatic Reaction Recruits Chiral Nanoparticles to Inhibit Cancer Cells” led by Xuewen Du from the Xu lab, “Semaphorin4D: a disease‐modifying therapy for epilepsy” led by Daniel Acker of the Paradis lab, “X‐ray transparent Microfluidics for Protein Crystallization” led by Achini  Opathalage from the Fraden lab and “New and Rational Catalyst Development for Green Chemistry”  from the Thomas lab.  Those interested in learning more about past SPROUT winners are invited to read this recent Brandeis NOW article. A list of additional winners, along with their executive summaries, is available on the Brandeis OTL website.

Teams seeking support for scientific projects which require bench research, lab space, and/or lab equipment are encouraged to submit an abstract prior to the March 7 deadline. The competition is open to the entire Brandeis community including faculty, staff, and students. The Office of Technology Licensing will conduct information sessions on Thursday, February 25th 11:30 a.m.‐12:30 p.m. in Volen 201 and on Monday, February 29th 1:00 p.m.‐2:00 p.m. at the Shapiro Science Center, 1st Floor Library. Staff will address the application process as well as specific questions and interested applicants are highly encouraged to attend.

More details regarding the SPROUT awards, process and online application may be found at bit.ly/SPROUT16.

Visualizing a protein decision complex in actin filament length control

Seen at the Gelles Lab Little Engine Shop blog this week, commentary on a new paper in Nature Communicationspublished in collaboration with the Goode Lab and researchers from New England Biolabs.

“Single-molecule visualization of a formin-capping protein ‘decision complex’ at the actin filament barbed end”

Regulation of actin filament length is a central process by which eukaryotic cells control the shape, architecture, and dynamics of their actin networks. This regulation plays a fundamental role in cell motility, morphogenesis, and a host of processes specific to particular cell types. This paper by recently graduated [Biophysics and Structural Biology] Ph.D. student Jeffrey Bombardier and collaborators resolves the long-standing mystery of how formins and capping protein work in concert and antagonistically to control actin filament length. Bombardier used the CoSMoS multi-wavelength single-molecule fluorescence microscopy technique to to discover and characterize a novel tripartite complex formed by a formin, capping protein, and the actin filament barbed end. Quantitative analysis of the kinetic mechanism showed that this complex is the essential intermediate and decision point in converting a growing formin-bound filament into a static capping protein-bound filament, and the reverse. Interestingly, the authors show that “mDia1 displaced from the barbed end by CP can randomly slide along the filament and later return to the barbed end to re-form the complex.” The results define the essential features of the molecular mechanism of filament length regulation by formin and capping protein; this mechanism predicts several new ways by which cells are likely to couple upstream regulatory inputs to filament length control.

Single-molecule visualization of a formin-capping protein ‘decision complex’ at the actin filament barbed end
Jeffrey P. Bombardier, Julian A. Eskin, Richa Jaiswal, Ivan R. Corrêa, Jr., Ming-Qun Xu, Bruce L. Goode, and Jeff Gelles
Nature Communications  6:8707 (2015)

The capping protein expression plasmid described in this article is available from Addgene.

Readers interested in this subject should also see a related article by Shekhar et al published simultaneously in the same journal.  We are grateful to the authors of that article for coordinating submission so that the two articles were published together.

DUB inhibitors _or_ why you should you eat your broccoli

Eat your broccoli!

We’re constantly bombarded by advice on which foods to eat or not eat, but skeptics among us often find compelling evidence for a convincing mechanism of how the foods promote health hard to come by – food has many components, and there are many different cells and metabolic pathways in those cells with which those components interact.

phenethyl isothiocyanate (a component of cruciferous vegetables)

phenethyl isothiocyanate (PEITC, a component of cruciferous vegetables)

Consider broccoli. It is well established that cruciferous vegetables have wide-ranging health benefits, apparently reducing cancer risks and lowering inflammation.  One set of phytochemicals responsible for the potent anti-cancer and anti-inflammatory properties are called isothiocyanates or ‘ITCs’.  It is now four decades since the discovery of ITCs, yet a molecular understanding of what ITCs do in a cell has proven elusive.

In a paper published this month in Cancer Research, Brandeis research scientist Ann Lawson, working in Liz Hedstrom’s laboratory, together with graduate students Marcus Long (Biochem) and Rory Coffey (Mol Cell Biol) and scientists from UbiQ and from Boston College, has shown that ITCs block the action of deubiquitinating enzymes (DUBs),  including the tumorigenesis-associated enzymes USP9x and UCH37, at physiologically relevant concentrations and time scales.

DUB inhibition provides a simple, unifying explanation that can account for many of the diverse health effects of ITCs. Understanding of how ITCs work at the molecular level may, one day, lead to new drug therapies for illnesses such as cancer, chronic inflammation, and neurodegenerative diseases.

Are you ready for your broccoli now? Me, I think I’ll have some kale sprouts.

Lawson AP, Long MJ, Coffey RT, Qian Y, Weerapana E, El Oualid F, Hedstrom L. Naturally occurring isothiocyanates exert anticancer effects by inhibiting deubiquitinating enzymes. Cancer Res. 2015

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