Stephanie Deluca Begins Term as BPS’s New Congressional Fellow

2015 DeLuca sci pol fellows close upCongress may still be out of town on its August recess (aka: campaigning), but the new class of AAAS Congressional Fellows, including BPS’s own Stephanie Deluca, are in Washington  and ready to get to work.  Today is the first day of orientation for the AAAS Science and Technology Fellowship Program,  which includes an intense two week orientation on congressional and executive branch operations followed by a year-long seminar series on issues related to science policy.  Once the orientation is complete, Deluca will spend a year working in a Congressional office on legislative and policy areas requiring scientific input.

It is important to note that while Deluca is serving as the BPS Congressional Fellow, she is an independent agent during the fellowship year.  This is extremely important in keeping  the divide between politics/government and special interest groups.  She is free to choose a placement that she desires, and works for that elected official for the term of her fellowship.

The Society’s leadership decided to offer the fellowship in 2015 in recognition that public policy increasingly impacts scientific research, and basic science literacy is increasingly needed to develop responsible policy. There are over 30 fellows participating in the program sponsored by AAAS as well as other professional societies.  Together, they provide important expertise across Capitol Hill.  Once the fellowship is over, some fellows return to research, while others continue working in science policy.  Regardless of the choice each fellow makes, the Society’s leaders are confident that the relationships forged between scientists and policymakers will continue.

DeLuca received her PhD in Chemical and Physical Biology from Vanderbilt University and has served as the Science Policy Fellow at the American Chemical Society (ACS) since September 2014. As for this next step in her career, she is excited about, “working in a fast-paced, high-stakes environment, where the work I do could have a real impact on people.”

If this peaks your interest, be sure to consider applying to be the next BPS Congressional Fellow.  Applications are due December 15, 2016.

 

 

 

 

Hiring, Firing, and Beyond: How to be an Effective Supervisor

At the Biophysical Society 60th Annual Meeting in Los Angeles, the Committee for Professional Opportunities for Women (CPOW) hosted a panel discussion called Hiring, Firing, and Beyond: How to be an Effective Supervisor.

The panel included Dorothy Beckett (University of Maryland), Kelly Knee (Pfizer), Prithwish Pal (Illumina), Rohit Pappu (Washington University in St. Louis), Rajini Rao (Johns Hopkins University), and Joanna Swain (Bristol-Myers Squibb). Session organizers Sudha Chakrapani (Case Western Reserve University), Gabriela Popescu (University at Buffalo), and Marina Ramirez-Alvarado (Mayo Clinic), facilitated the discussion, which is summarized below.

Panel members stressed that populating the lab with talented, creative, and hard-working trainees is critical to any PI’s success. Whether looking to hire students or postdocs, it is essential to start with a detailed and accurate description of the position. This helps you as the PI to focus on the most important characteristics of the person you are looking for; it also helps applicants to self-select. For a graduate student, highlight techniques the advanced techniques to be used; for a postdoctoral position, highlight opportunities for additional training and career development. Once you are satisfied with the description, send it to colleagues who may know good candidates, and add it to your website. Placing ads in magazines like Science and Nature generate many responses, but many will be irrelevant.

Once you have identified a few interested applicants, you are faced with the challenge of determining who will best fit in with your lab environment and culture. If you have a rotation system for students at your university, use your rotations wisely. Spend time in the first two weeks with the student talking about what question he/she should be looking to answer, rather than the everyday minutiae of the position. Let them know your working style and that of your lab members. Watch, assess, and monitor how the student fits in and adds to the lab.

If you do not have the luxury of time with a potential trainee, ask behavioral questions in your interviews. One prompt to give applicants is, “Tell me about a time you had to deliver something by a certain time and it did not go well.” Let them tell the story and keep asking questions as they talk.

Plan for candidates to spend time with both senior and junior members of the lab so that you can evaluate how they will interact with both; ask your team members for their evaluation of the candidate.

Another challenge you will face as the lab director, is to set boundaries around work schedules. It is helpful to keep in mind that productivity does not always correlate with a magic number of hours spent working in the lab, even if that’s where data are collected and knowledge discovered! Some students can be very productive with a 9-to-5 schedule; whereas others may hang in the lab constantly without accomplishing much. Put more weight on the results of their work than the number of hours they are working.

You may find that a dedicated student has difficulty with a particular task. Hopefully you can help them to overcome the difficulty. Remember that they do not have the necessary experience and may lack perspective; be patient and curious. Start by giving the student small tasks and evaluate how proficient and efficient they are in accomplishing them; this will give you an idea of the roadblock they are facing. Some students have “experiment-phobia” and talk themselves out of taking action; give them license to have things not work out right away. Others feel that they need to be perfect and spend too much time on inconsequential aspects of the work, or proceed at an exceedingly slow pace to avoid mistakes. Emphasize to them that it is okay to fail by telling stories of your own mistakes. This will help them realize that their mistakes can be fixed and are not the end of the world. Give the students a checklist of things that could have gone wrong so that they can try to figure issues out on their own before bringing you in. This will give them a greater sense of ownership over their experiments.

It is of paramount importance to make your expectations clear from the beginning and to hold people accountable to these. If a trainee becomes toxic to the environment in the lab, seek a second opinion before taking irreversible actions. Talk to a senior colleague about your concerns; make sure your expectations are reasonable and have been communicated clearly. Once you are clear that the trainee is simply a poor fit, do not wait too long to ask them to leave. Yes, it is never pleasant or easy to let people go; however, keep in mind that the price your lab pays may be a steep one.

Once you made the decision to let someone go, talk to them in private. Be pragmatic rather than placing blame, and always be civil. Give them enough time to find a new position. If you are asking a postdoc to move on before his/her contract is up, make sure that you have documentation about their behavior.

In keeping a productive and positive lab environment be mindful not to transfer your stressors onto your lab members. Instead find a peer or a senior colleague to talk these over; your stress can negatively affect both your home and your lab activities. Do not put undue pressure on lab members and avoid blaming them for all that goes wrong; such a highly demanding environment may inadvertently encourage someone to fabricate data, which is every PI’s nightmare! However, also stay away from micromanaging; this is rarely well-received and often takes away from a trainee’s time at the bench.

Whether you are hiring, firing, or managing people keep in mind that trainees join your team to learn from you, to further their skills, and to discover knowledge, while like every other person they have their own challenges to overcome, and that both their aspirations and difficulties are just as important as your own. Treat your team members as co-discoverers rather than employees and inspire them with your good will, patience, and enthusiasm.

Members of the panel and the audience alike agreed that being an effective supervisor requires skills that cannot be gained overnight. One must be patient, willing to learn from mistakes and seek council from a diverse network of colleagues, and aspire to move from managing trainees to truly leading a team.

Where do the Candidates Stand on Science?

White-House-SD-Qs-Banner.jpg2016. An Election year in the United States. It’s nearly impossible to turn on the television, pull up news on the computer, or scan your social media accounts without seeing some sort of political news. Often the coverage is about the horse race aspect of the election— polling numbers, for example—or the candidates’ whereabouts on the campaign trail.  Occasionally the coverage is policy based.  Rarely, though does this include a candidate’s views on scientific issues.

Earlier this month ScienceDebate.org released 20 science questions to which it would like the Presidential candidates to respond.  The Biophysical Society assisted in the creation and vetting of the questions and endorsed the final list.  Along with other leading science organizations, the Society would very much like to hear where Clinton, Trump, and the third party candidates stand on these important questions that touch on vaccines, climate change, jobs, and research.  The questions received attention from the press, but the candidates have yet to respond.  We hope that they will in the coming weeks.  We also hope to see some of these questions posed in the national debates.

Here are the questions.

ScienceDebate.org was originally started in late 2007 to garner support for science issues to be included in Presidential debates prior to the 2008 election. Candidates Obama and McCain did go on record with responses to the questions then; here’s hoping Clinton and Trump let us know where they stand!

Biophysical Society Summer Research Program: The Time of Your Life

li_alexMy name is Alex Li. I am a rising third-year undergraduate student at UNC-Chapel Hill, majoring in B.S. Chemistry with a focus in biochemistry. I first found my love of chemistry in high school after taking AP Chemistry and now I wish to specialize my interests in organic chemistry after taking a two-semester sequence of it with Michael Crimmins. I have always loved science since I was a kid – it led me to questioning “why” and “how” to every scientific phenomenon, as if I am the detective trying to fit every piece of a jigsaw puzzle. In my free time, I like to play the piano (classical), listen to new music (rap), and try new outdoor adventures (skydiving). I plan to pursue a dual-DDS/DMD and PhD in dentistry and organic chemistry in the future, as I am interested in career options such as clinics, industry, and academia.

I first heard about the Biophysical Society Summer Research Program from Howard Fried, who strongly suggested that I should apply to this program, because he wanted me to get exposed to the field of biophysics. I chose this program because it lasted for so long and I wanted to get the most out of learning and research this summer.

I worked this summer under Kevin Weeks, under whom I researched about different conformations of the RNA genome within satellite tobacco mosaic virus (STMV). This work is related to biophysics in that the research can be applied to visualize RNA structure and dynamics in vivo with high-throughput analytical methods (i.e. x-ray crystallography and cryo-electron microscopy). By understanding the biomechanics of the STMV viral life cycle (i.e. entry, disassembly, replication), we can obtain the knowledge to develop antiviral drugs that are effective against more complex viruses (i.e. adenovirus, rhinovirus, poliovirus) that have the same structure as STMV’s. It was a rewarding and challenging summer in Kevin’s lab, especially working entirely independently and discovering literature sources to plan out my experiments.

What I liked so much about BPS Summer Course was that it is different from what other REUs [Research Experiences for Undergraduates] provide to motivated science students during the summer. It is a combination of everything: lectures/recitations, career panel workshops, seminars, lab tours, and fun social events! The lectures provided a brief overview, but intensive insight, into different fields of biophysics from UNC faculties; we also had fantastic TAs who helped us understand biophysics since it was confusing a lot of the time. There were workshops that gave helpful advice and learning tools for graduate school or MD/PhD admission process, GRE testing, abstract and personal statement writing, and much more. Different faculties from universities across the United States gave seminars about their biophysics research, which were very engaging and interactive. We also got to tour different lab facilities across UNC’s campus (which I never knew about!) to see some of the coolest science equipment, such as atomic force microscope. Some of the best memories I have made this summer was during the Emerald Isle beach trip – a social event that should be continued for future classes!

Overall, I am beyond elated to say that this summer program was a blast – both educationally and socially. I am glad I applied and I strongly recommend others to do so in the future. I will dearly miss all of the friends I have made this summer and like to thank all of the BPS Summer Course coordinators that helped made this summer possible.

-Alexander Y. Z. Li, 2016 Biophysical Society Summer Research Program Fellow

Epithelial Folding: How Planar Cell Polarity Regulates 3D Organogenesis

BPJ_111_3.c1.inddIt is a nice season to enjoy the river by canoeing or kayaking. But do you know that mammalian eggs also drift over a deep channel? This channel, or epithelial folds, is in a tubular organ named the oviduct, or Fallopian tube in humans, connecting the ovary and the uterus.

Viewing the cover image, you too can experience going through the oviduct from the point of view of an egg. The epithelium of the oviduct in the image was obtained by a mathematical simulation. The epithelial folds are straight and align longitudinally along the ovarian-uterine axis in mice and other species of animals. Previously, we reported that a Planar Cell Polarity (PCP) factor Celsr1 regulates fold patterning in mice. But the mechanisms connecting PCP with the well-patterned alignment of the epithelial folds are still unknown.

Here, we analyzed the mechanical regulation of the epithelial fold patterning by mathematical modeling where the epithelium was defined as an elastic sheet. We found that PCP could mechanically regulate the three-dimensional morphogenesis via the polarized cell array. Furthermore, our model scheme is also useful for analyzing mechanical effects on epithelial morphology generally. Our simulation could recapitulate the morphology of various types of epithelial folds, some of which can be found in other organs in vivo.

A sophisticated three-dimensional morphology is important for the organ’s function, but we are still far from a comprehensive understanding of the mechanism to build it.  The oviduct is not only where we come from, but is also a good place to start our scientific journey.

-Dongbo Shi, Hiroshi Koyama, Toshihiko Fujimori

On the BPS Code of Conduct, Anti-Harassment Policy

Sharona Gordon, Professor, University of Washington and Editor-in-Chief, Journal of General Physiology shares her views on sexual harassment in science and the code of conduct and anti-harassment policy the Biophysical Society instituted in 2015.

In my view, a successful society must protect the interests of the most vulnerable among its population. In our global society that means the poor, the sick, the disenfranchised, and any others who do not enjoy the privilege those of us in the upper echelons take for granted. In a professional society such as the Biophysical Society (BPS), the most vulnerable among us are trainees. Students and postdoctoral scholars depend entirely upon the support of more established scientists for access to mentoring, experimental resources, introduction to a broad network of other scientists, and letters of recommendation required for career advancement. For the vast majority of us, this power we hold over trainees is the power to protect. However, for some among us, this power is used to intimidate and exploit.

Sexual harassment has been in the news in the last few years due to some particularly horrifying and long-lasting patterns that came to light. The behavior of exoplanet astronomer Goeff Marcy at UC Berkeley seems so surreal that it is human nature to dismiss it as an exception that must surely be exceedingly rare. To illustrate this, a colleague I ran into at a seminar, who happens to be a department chair, asked me whether I thought anything like the Marcy incident could happen at our institution, the University of Washington. As if to underscore my answer that I was sure it was happening even as we sat there and discussed science, months later a UW colleague named Michael Katze was revealed to have led a decades-long sexual circus in his lab. If institutions can be blind to such egregious cases spanning years, what hope is there for getting institutions’ attention for acute, more mundane incidences of harassment?

Is sexual harassment at BPS-sponsored events a problem? Yes because it happens and yes because it undermines the free exchange of scientific ideas our meetings and events are meant to promote. Although I have not seen data examining the collective experiences of our members, I have personally experienced sexual harassment at the annual meeting. I have avoided events at which a past harasser was likely to be present. In addition, I have observed sexual harassment at the meeting and intervened in sexual harassment at the meeting. Even if my direct experience of harassment at BPS sponsored-events were unique, our members come from a world in which harassment based on gender, race, ethnicity, sexual identity, religion, and other factors is commonplace. Policies governing harassment are even more important at professional society events, where scientists of all ranks mix more freely and the protections of the academy may seem distant. In short, sexual harassment happens at BPS-sponsored events, as it does at events sponsored by all professional societies, and the reduced contributions from those affected by harassment diminish the value of the meetings for all.

For both the Marcy and Katze cases, the financial benefit to the institutions of looking the other way may have been a factor in the longevity of the harassment. Professional societies, in contrast, are not direct beneficiaries of the millions of dollars in grant money brought in by established faculty. Membership dues paid by one person make little difference to the financial health of the professional society, so that societies may be in a unique position to address harassment without the conflict-of-interest that arises from the economic value of a given faculty member. I believe that professional societies thus have an obligation to proactively educate their members about harassment and ensure it is not tolerated among their ranks.

When the Marcy case was first reported in the popular press, I wondered whether my professional society, BPS, had an anti-harassment policy in place. What I found was that BPS was among the majority of professional societies in its lack of policies governing professional behavior and prohibiting sexual harassment. As a member of BPS for more than 20 years, a former member of Council, Co-Chair of the Program Committee, and past member of the CPOW, Nominations Committee, and Thematic Meetings Committee, I felt it was my responsibility to help BPS correct this deficit. I wrote a letter to the BPS leadership explaining the need for an anti-harassment policy and pointing to the bylaws and anti-harassment policy of the American Astronomical Society as a model for its anti-discrimination language and its policy governing its meetings and events.

My confidence that my BPS colleagues would take up my charge was satisfied rapidly. I wrote my letter in October, 2015 and a policy was in place in time for the 60th Annual Meeting in February, 2016. The BPS Code of Conduct and Anti-Harassment Policy covers the definition of harassment, outlines an investigative process, specifies disciplinary actions, and an appeals process. I am proud of BPS for taking this step forward in protecting the interests of trainees and others vulnerable to harassment and intimidation. I am proud to be a member of a Society that strives to create a safe, welcoming environment for the exchange of scientific ideas. I would also encourage all members to participate actively in BPS because, as a collection of individual members, each of us can make a difference.

Connect with the author on Twitter @ProfSharona.

Biophysics on World Hepatitis Day 2016

July 28 is World Hepatitis Day. Viral hepatitis is inflammation of the liver caused by a virus. There are five different hepatitis viruses, hepatitis A, B, C, D and E. Hepatitis C affects approximately 250 million people worldwide. We spoke with Jiawen Li, University of Texas at Austin, Institute of Cellular and Molecular Biology, about her research related to hepatitis C, for which there is currently no vaccination.  

What is the connection between your research and hepatitis C?

Here in the Johnson lab we use transient-state kinetic approaches to characterize viral polymerases, specifically to measure nucleotide specificity, polymerase fidelity and dynamics. More importantly, we apply these methods to understand the mechanisms of action of nucleoside analogs and non-nucleoside inhibitors that are developed to target viral polymerases. For example, to combat HIV, reverse transcriptase is primarily targeted for anti-AIDS therapy. As the RNA-dependent RNA polymerase for Hepatitis C virus, NS5B is considered an important target for effective antivirals as well. Thus the focus of our research is to develop assays to determine kinetic parameters governing RNA dependent RNA replication by NS5B and establish the mechanisms of action and efficiency of various clinically relevant anti-HCV drugs.

Why is your research important to those concerned about hepatitis C?

Hepatitis C affects approximately 250 million people worldwide and chronic infection can lead to hepatitis, liver cirrhosis, and cancer. There is no vaccine available, but combination therapies with direct-acting antivirals including nucleoside analogs and non-nucleoside inhibitors targeting NS5B have been recently advanced and have dramatically improved the potency of HCV treatment. Surprisingly, besides the identification of binding site on NS5B, very little is known about the inhibition mechanisms of drugs that are currently on the market. Two pharmaceutical companies, Gilead Science and Alios Biopharma, have generously provided us with some of their inhibitors to study. Our primary goal is to analyze a handful of these inhibitors in depth to establish their mechanisms of inhibition and to set evaluation guidelines for the effectiveness of each class of inhibitor. Ultimately, we want to apply our methods to each FDA-approved inhibitor for HCV treatment to aid information for the development of even better therapeutics.

How did you get into this area of research?

With a bachelor’s degree in Biochemistry, I was accepted into the Biochemistry graduate program at UT Austin in 2011. During my rotation in the Kenneth Johnson lab, I was fascinated by transient-state kinetic methods such as combining rapid quench-flow and stopped-flow techniques to accurately measure and analyze nucleotide incorporation by HIV RT. Of course I immediately joined the lab and I was very enthusiastic to work on other viral polymerases. The hepatitis C viral RNA-dependent RNA polymerase, NS5B, is known to catalyze de novo RNA synthesis, which means RNA replication is divided into two distinct mechanistic phases: initiation and elongation. Previous studies in our lab along with other groups in the field have made tremendous efforts to develop assays for efficient NS5B replication, but were always hindered by the slow and inefficient initiation phase. Therefore, although the crystal structure of NS5B was solved a decade ago, kinetic characterization of enzyme mechanism, specificity and fidelity are limited, and little is known about the mechanistic basis for inhibition. Finally in 2012, Zhinan Jin, who graduated from our lab and worked for Roche at the time, succeeded in developing conditions for formation of highly active HCV elongation complex. I then continued the work he has accomplished and further optimized the kinetic assays for NS5B inhibition analysis.

How long have you been working on it?

It has been four years since I started working on HCV NS5B in 2012 as a second year graduate student here at UT Austin. I know several lab members had tried to establish conditions for efficient NS5B replication over a decade ago. I am glad this project is brought back to life again!

Do you receive public funding for this work? If so, from what agency?

Yes, we received funding from the Welch Foundation and the National Institutes of Health.

Have you had any surprise findings thus far?

Yes, we have had several surprise findings along the way. Firstly, we now have successfully developed robust kinetic assays to monitor RNA replication by NS5B from initiation to elongation. To our surprise, once the elongation complex is formed, it is extremely stable with half-life of more than a week, which makes the crystal structure of NS5B ternary complex highly promising to obtain in the near future.

Secondly, we have been able to establish modes of action for four classes of non-nucleoside inhibitors. One class of NNIs, the thumb site II inhibitors (NNI2) were shown to be most interesting. NNI2 do not significantly block HCV initiation or elongation; rather they act as allosteric inhibitors to block NS5B transition from initiation to elongation, which is thought to occur with a significant change in enzyme structure. To further examine this allosteric inhibition, we collaborated with Dr. Patrick Wintrode from the University of Maryland and his postdoc Daniel Degrede who mapped the effect of NNI2 inhibitors on the conformational dynamics of NS5B using hydrogen-deuterium exchange kinetics. HDX shows that NNI2 rigidifies an allosteric network extending up to 40 Å from the inhibitor binding site to enzyme active site, providing the rational for blocking NS5B transition at the molecular dynamics level.

NNI2-NS5B HDX (Jiawen Li)

Peptic fragments resulted in significant decrease in HDX upon NNI2 (magenta sticks) binding are shown in dark blue. Rigidification of a large network of enzyme dynamics was observed starting from inhibitor binding site throughout the protein, especially surrounding the enzyme active site, suggesting a long range allosteric effect from inhibitor binding on NS5B conformational change.

Meanwhile, we also explored the mechanisms of NS5B inhibition by nucleotide analogs. We found that both pyrophosphate and NTP mediated excision of incorporated nucleoside analogs were relatively fast reactions, suggesting the important role of pyrophosphorolysis in evaluating the effectiveness of chain-terminating inhibitors. In fact, wild-type NS5B polymerase catalyzes the nucleotide-dependent excision reaction faster than mutants of HIV reverse transcriptase that have evolved to overcome inhibition of nucleoside analogs. This is a significant problem for design of nucleoside analogs to treat HCV infections. We are in the process of publishing this work soon.

What is particularly interesting about the work from the perspective of other researchers?

Our detailed mechanistic studies have provided a fundamental understanding of RNA-dependent RNA replication by HCV NS5B and established the mechanisms of action of different anti-HCV drugs. We hope our experimental and analytical methods will benefit other researchers for studying HCV polymerase or similar viral polymerases and eventually assist screening and design of more effective inhibitors to combat HCV and other viral diseases.

What is particularly interesting about the work from the perspective of the public?

It is great news knowing that more and more anti-HCV drugs are being developed and approved by FDA. With the platform we built for inhibitor analysis, we would like to incorporate more inhibitors into our study and determine their biochemical role of inhibition. We think our work will help providing insights for the development of drugs that are safer and effective against broader range of HCV genotypes.