The Genetics Training Grant hosts a panel discussion and lunch focused on careers outside academia

This past Monday, April 29th, students and post-docs, eager to learn more about careers outside of academia, had the opportunity to hear from, and question, panelist who have successfully harnessed their PhD experience to excel in non-academic careers. The event, hosted by the Genetics Training Grant, brought together panelists from several different fields, including scientific publishing, pharmaceutical research, consulting, and intellectual property law. The panelists were Priya Budde, Reviews Editor, The Journal of Cell Biology; Sadanand Vodala, Research Scientist, ARIAD Pharmaceuticals; Derek Buhl, Principal Scientist, Pfizer Neuroscience; Peter Bak, Consultant, Back Bay Life Science Advisors; and John Garvey, Partner, K&L Gates LLP. Each panelist spoke about their background in academia, how they made the transition to their current position, and fielded numerous questions from the audience both during the panel and at the networking lunch that followed.

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 (graduates 2002 and beyond, n=200)

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?

John Lowenstein (1926-2012)

Professor Gregory Petsko delivered the following tribute for John Lowenstein at Brandeis University Faculty Meeting late last year:

lowensteinJohn Lowenstein, who passed away from pancreatic cancer on November 3, 2012 at the age of 86, joined the Brandeis community in 1958 as a Senior Research Fellow, and became a member of the faculty two years later. From 1974-1995 he held the Helen Rubenstein Chair in Biochemistry; and he was also chair of the department in the 1990s.  John was not only a highly accomplished scientist; he was also an extraordinarily literate man, well versed in English, Russian and German literature, and a staunch devotee of opera, too. Even after his retirement in 2008, he continued to pursue his research interests and to work with students – he continued, in fact, to supervise an undergraduate until a few weeks before he died.

Those are the bare bones facts.  Let me tell you the story.  Many of you may know that John was one of the first members of the Biochemistry Department.  He came in the fall of 1958.  He’d been a Fellow at Oxford University, a position that allowed him a lot of independence, so when Mary Ellen Jones persuaded Nate Kaplan, the legendary founder of the department, to offer him a job, John already had the beginnings of a research program going.  He accepted the offer because America was, at that time, a better place for his wife, who was a clinician.  So he actually came here as an accompanying spouse (he once told me that he considered that a surprisingly liberated role for a man in the 1950s).  Before leaving England, he wrote to both the NIH and NSF to ask if it was OK for a foreigner to apply for a research grant; when they said it was, he wrote two different proposals, one to each of them.  He thought it was unethical to ask for salary on a grant, so he didn’t.  To his surprise, both grants were funded, so he ended up with full research support but no salary support.  Clearly, as we all know, Brandeis is a perfect choice for someone who wants to work without a salary!

Somebody then suggested he write a fellowship proposal, which he did, to the Helen Hay Whitney Foundation.  That was at the time, and still is, one of the most prestigious fellowships in the sciences.  Of course, he got that too, so when he finally showed up at Brandeis as, in essence, a postdoc, he had two grants and full salary support – more than most of the faculty!  Three weeks after he arrived, he started to lecture in Biochemistry on the 3rd floor of Kalman.  John once told me he was delighted that he was able to say that he had outlived that building!  Within 6 years of his arrivak, the Biochemistry Department was listed among the top 10 departments in the country, and it remained there until the mid-70s, when the practice of ranking departments stopped. 

After less than 2 years as a Whitney Fellow at Brandeis, John was already getting offers of faculty positions from other institutions for his work on nonenzymatic phosphate transfer by ATP, a very important process that he discovered.  Kaplan talked him out of considering most of them, but when one came from Tufts, Kaplan immediately promoted him to assistant professor.  By then, John had overcome his ethical objections to putting his salary on research grants…

purine nucleotide cycle

By the early 1970s, John had worked out the function of the important enzyme AMP-deaminase, the founding member of a family of enzymes that are very important in health and disease.  He then went on to do something only a handful of scientists have ever done: he discovered a metabolic pathway, the purine nucleotide cycle that AMP deaminase functions in.  This ought to be called the Lowenstein Cycle, but John once told me that if you discover something so important that you don’t have to name it after yourself, you’ve really done something special!

John always ran a small research lab but in many ways he ran the department for quite some time.  He had served on every possible departmental committee, popular and unpopular, sometimes all at the same time, or at least it seemed that way to him!  He was Chair of the Department in the early 1990s.  When I became chair of the department, a few years ago, I immediately sought out his advice.  He said, “Greg, my advice to you is to start drinking heavily.” 

He taught Biochem 101, the department’s signature graduate course, for many years, and then led the movement for the department to teach undergraduates.  Putting his money where his mouth was, he then taught the basic undergraduate course, Biochem 100 – sometimes two sections a day – until 2005. 

John had three sons; his middle son is a scientist at Johns Hopkins; the youngest is a professor of music, and his oldest is a businessman.  John was very, very proud of his family, but said to me on more than one occasion that the major place in his life, outside that family, was Brandeis.  It’s no accident that, for many years, John was the faculty member all the graduate students went to for advice.  He had a pilot’s license and used to fly sailplanes, but I think the students were quick to identify someone who was always good at keeping his feet on the ground. 

John once said that if he were independently wealthy he would still do what he does.  I was thrilled to hear that because it meant that, even after becoming emeritus, John would still be around a lot, and he was.  The best raconteur in the department, John had a warm, wise and often dryly funny story for every occasion.  It was part of the way he imparted his enormous common sense.  No one here meant more to me as a colleague, a friend, and a role model. He said to me that, when he retired, it meant the Biochemistry Department was going to gain in reputation, because he was going to have much more time for research… Few did it better, or with more style. 

On the occasion of his retirement, I asked John to sum up his years at Brandeis.  He just smiled and said, in his typical understated way, “I like to think I’ve been a cog in something worthwhile.”  We should all be such a cog!

Remembrances may be made to the American Jewish Joint Distribution Committee, www.jdc.org.

Lab flag competition

Brandeis Life Sciences groups combined graphic design, photoshop, latin composition, and punnery in a “lab flag” competition at the holiday party on December 15. Pick your favorite from the entrants below!

 

Pieter Wensink (1941-2012)

Professor Jim Haber presented the following memorial tribute at Faculty Meeting on Nov 8, 2012:

Professor Emeritus Pieter Croissant Wensink passed away on October 2, 2012 in Wellesley, MA. Pieter was born in Washington, DC, in 1941, and grew up in Bethesda and Chevy Chase, MD. He attended Lawrence College in Appleton, WI, but like many young people in the 60s, dropped out. He ended up working in a laboratory at Johns Hopkins, where he discovered a passion for science. He never got his BA, but by taking night courses Pieter got himself accepted as a graduate student at Johns Hopkins, where he received his PhD in Biology in 1971, working with Don Brown, a pioneer in studying the regulation of gene expression in frogs. Pieter then went to Stanford, where he did post-doctoral work with David Hogness. At Stanford, Pieter got in on the ground floor of the new recombinant DNA technology. He published, with Hogness, a landmark paper entitled “A system for mapping DNA sequences in the chromosomes of Drosophila melanogaster” – the fruit fly.

In 1975 Pieter came to Brandeis as an Assistant Professor in the Rosenstiel Center and in the Department of Biochemistry, bringing to Boston the then-rare and prized knowledge of how to clone genes. I remember clearly in 1976 when an MIT professor, David Botstein, and his postdoc, Tom Petes, camped out at Brandeis for several weeks learning from Pieter how to clone yeast genes. Their collaboration resulted in another major paper “Isolation and analysis of recombinant DNA molecules containing yeast DNA.” Soon thereafter Matthew Mesleson arrived from Harvard, to collaborate with Pieter on the “Sequence organization and transcription at two heat-shock loci in Drosophila.” All of these papers were pioneering works.

Pieter also taught these “dark arts” to the people in my lab and launched us and others at Brandeis on the way to understanding the mysteries of chromosome architecture and gene regulation. In 1981 Pieter also wrote a book in collaboration with his Biochemistry colleague Bob Schleif: Practical Methods in Molecular Biology.

Pieter’s own work, carried out with a series of superb graduate students, focused on genes that encode the proteins that make up the yolk of Drosophila eggs. The study of these genes revealed the complicated way that yolk protein genes are turned on only in females and only in their ovaries. Many of Pieter’s students are now Professors in their own right at major universities around the country.

In the early 1990s Pieter was diagnosed with a benign brain tumor – a meningioma – that required two surgeries to extirpate. Probably his tumor was the result of the now-impossible-to-believe treatment of a ringworm infection with X-rays when he was about 2 years old. The second operation left him unable to concentrate as he had, and Pieter, sadly, decided that he could no longer run his lab or give the clear lectures had had been offering. So he left Brandeis as an emeritus Professor with a medical disability. Pieter was remarkably calm and accepting about his situation. He decided to pursue a long-deferred passion to paint, and some years ago he earned his BFA with distinction in painting from the Massachuetts College of Art. Altogether, Pieter had 5 operations on the cancers that led to his death.

Pieter’s greatest joy in life was his family. He was married to Dorothy E. (Perry) for 43 years and was the devoted father of Tom, Alan and Joe (who recently earned his PhD in English from Brandeis).

Most of you never met Pieter, so I thought it would be good to see Pieter and some of his colleagues as we looked in the late1970s (Pieter, Michael Rosbash, Marion Nestle (now oft-interviewed nutritionist at NYU), myself, and David DeRosier). And to see two of his paintings. He was a fine man.

 

Deciding the fate of a stalled RNA polymerase

Ever wondered what happens when the transcription machinery runs into a DNA lesion or a protein roadblock? Alexandra M. Deaconescu, corresponding author and research associate in the Grigorieff laboratory together with HHMI Investigator and Biochemistry Professor Dr. Nikolaus Grigorieff and Dr. Irina Artsimovitch (Ohio State University) address this question in a new review “Interplay of DNA repair with transcription: from structures to mechanisms” featured in the latest issue of Trends in Biochemical Sciences. The review describes emerging mechanisms of transcription-coupled DNA repair with emphasis on the bacterial system.

Materials in Motion: Engineering Bio-Inspired Motile Matter

Life is on the move! Motion is ubiquitous in biology. From the gargantuan steps of an elephant to the tiniest single celled amoeba, movement in biology is a complex phenomenon that originates at the cellular level and involves the organization and regulation of thousands of proteins. These proteins do everything from mixing the cytoplasm to driving cell motility and cell division. Deciphering the origins of motion is no easy feat and scientists have been studying such complex behavior for quite some time. With biology as an inspiration, studying these complex behaviors provides insight into engineering principals which will allow researchers to develop an entirely new category of far-from-equilibrium materials that spontaneously move, flow or swim.

In a recent report in the journal Nature, a team of researchers from Brandeis University consisting of Tim Sanchez, Daniel T. N. Chen, Stephen J. DeCamp, Michael Heymann, and Zvonimir Dogic have constructed a minimal experimental system for studying far-from-equilibrium materials. This system demonstrates the assembly of a simple mixture of proteins that results in a hierarchy of phenomena. This hierarchy begins with extending bundles of bio-filaments, produces networks that mix themselves, and finally culminates in active liquid crystals that impart self-motility to large emulsion droplets.

Their system consists of three basic components: 1) microtubule filaments, 2) kinesin motor proteins which exert forces between microtubule filaments, and 3) a depletion agent which bundles microtubule filaments together. When put together under well-defined conditions, these components form bundled active networks (BANs) that exhibit large-scale spontaneous motion driven by internally generated active stresses. These motions, in turn, drive coherent fluid flows. These features bear a striking resemblance to a biological process called cytoplasmic streaming, in which the cellular cytoskeleton spontaneously mixes its content. Additionally, the system has great potential for testing active matter theories because the researchers can precisely tune the relevant system parameters, such as ATP and protein concentration.

 

The researchers also demonstrate the utility of this biologically-inspired synthetic system by studying materials science topics that have no direct biological analog. Under dense confinement to an oil-water interface, microtubule bundles undergo a spontaneous transition to an aligned state. Soft matter physics describes such materials as liquid crystals, which are the materials used to make liquid crystal displays (LCDs). These active liquid crystals show a rich variety of dynamical behavior that is totally inaccessible to their equilibrium analogs and opens an avenue for studying an entirely new class of materials with highly desirable properties.

Lastly, inspired by streaming flows that occur in cells, the researchers encapsulate the bundled active networks into spherical emulsion droplets. Within the droplet, microtubules again formed a self-organized nematic liquid crystal at the oil-water interface. When the droplets were partially squished between glass plates, the streaming flows generated by the dynamic liquid crystals lead to the emergence of spontaneous self-motility.

This research constitutes several important advances in the studies of the cytoskeleton, non-equilibrium statistical mechanics, soft-condensed matter, active matter, and the hydrodynamics of fluid mixing. The researchers have demonstrated the use of biological materials to produce biomimetic functions ranging from self-motility to spontaneous fluid flows using fundamentally new mechanisms. Additionally, the experimental system of bundled active microtubules is poised to be a model for exploring the physics of gels, liquid crystals, and emulsions under far-from-equilibrium conditions.

To see more videos from the Dogic lab at Brandeis University, check out their YouTube page.

Materials Science poster session

The NSF funded Materials Research Science & Engineering Center (MRSEC) received its 5 year review on Oct 11-12, 2012 when a panel of 5 scientists and 2 NSF officials visited Brandeis and kicked the tires of our Center. The highlight of the review was lunch between the panelists and 20 MRSEC graduates students and postdocs and the poster session, shown here, in which 30 posters describing research in the Center was presented to the panel. The four MRSEC thrusts were represented in the poster session: Active Matter, Chiral Self-Assembly, Oscillating Chemical Dynamics, and Confined Polymers, plus posters on our Seeds and Facilities. Join us again in Spring for our on-campus retreat.
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A Cellular Rocket Launcher links Actin, Microtubules, and Cancer

Cells contain thousands of protein “micromachines” performing a bewildering number of chemical reactions every second. The challenge for biologists in the 21st century is to integrate information about multiple – or even all – proteins into holistic models for the entire cell. This is a daunting task. The addition of any new component to a system can alter the behavior of the components already there. This phenomenon is especially familiar to biologists studying the cytoskeleton, a complex system of protein filaments that provide the force for cell division and migration, among other things. The building blocks of the cytoskeleton are simple proteins called tubulin and actin that assemble into a remarkable variety of shapes depending on context. While the basic chemistry of this assembly process has been understood in purified systems for decades, how it happens in cells is not well understood. For example, growth of actin filaments is a two-step process: nucleation, or the formation of a new filament, and elongation, or the extension of that existing filament. Both steps happen just fine when actin is present in pure form in a test tube. In cells, however, proteins called profilin and capping protein block these two steps, respectively. Nucleation and elongation can only occur because other proteins overcome these blocks. Thus, a faithful experimental system to study actin assembly as it would occur in a living cell requires – at a minimum – five purified proteins.

One technological advance of great importance is the ability to literally see single molecules (in this case proteins) using advanced fluorescence imaging. In such an experimental system, many details can be captured. In a recent publication in Science, Dr. Dennis Breitsprecher and colleagues in the Goode and Gelles labs, undertook this challenge and directly visualized the effects of key regulatory proteins helping actin proteins nucleate and grow into filaments in the presence of both profilin and capping protein. A previous study from the Goode lab had shown that two proteins, called APC and mDia1, together stimulate the growth of actin into filaments (Okada et al, 2010). In the present study, Breitsprecher and colleagues examined the mechanism by which APC and mDia1 overcome the profilin and capping protein-imposed blocks. To do this, they ‘tagged’ actin, APC and mDia1 with three different fluorescent dyes, each of a different color, and then filmed these molecules (using triple-color TIRF microscopy) in the act of building an actin filament to learn precisely what they are doing.

The authors began by imaging APC and actin (2 colors) at the same time. APC formed discrete spots on the microscope slide, and growing actin filaments emerged from them, suggesting than APC nucleates actin filament formation. As the filament emerged from the APC spot, APC stayed where it was: remaining stably associated at the site of nucleation. Next, the authors added dye-labeled mDia1 to the system, and observed mDia1 molecules staying attached to and ‘riding’ the fast-growing end of actin filament, while protecting it from capping protein.

The most remarkable result came when they visualized all three labeled molecules together (actin, APC, and mDia1). What they saw was that APC and mDia1 first come together in a stable complex even before actin arrives. Then APC recruits multiple actin subunits to initiate the nucleation of a filament. This complex was resistant to the blocks imposed by both profilin and capping protein. As the filament grew from the APC-mDia1 spot, mDia1 separated from APC and stayed bound to the growing end of the filament – protecting it from capping protein while it grows. Thus, even though APC and mDia1 have different activities, participating in different stages of the growth of a filament, they associate together before actin even arrives, likely so that once the actin filament is born, it is immediately protected from capping protein. This mechanism has been compared to a rocket launcher: APC is the launch pad for an actin filament, which is then propelled forward by mDia1.

Rocket launcher images and cartoon

Rocket launcher mechanism for APC and mDia1 nucleation. Left: Microscopic image of a growing actin filament. APC stays put while mDia1 remains associated with the fast growing end. Right: Model for the rocket launcher mechanism.

The new study provides great detail of the system: for example, the number of APC subunits required to nucleate actin filaments was determined, and the growth rate of actin filaments in the presence and absence of all the other components was measured. Ultimately, all of these data will be required to put together a detailed model of how actin filaments grow inside of real cells: details that would be difficult or impossible to obtain without employing single molecule analysis.

For the future, the authors have set their sights on even more challenging experiments aimed at elucidating the mysterious link between tubulin and actin fibers. APC and mDia1 are implicated in this linkage in living cells, but almost nothing is known about how they physically link and/or communicate information between the two systems. Since APC is mutated in some 80% of colon cancer tumors, understanding its multiple roles is of clinical as well as intellectual importance. This will be an exciting, if challenging, endeavor for the future.

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