Histone Tails on the BiophysJ Cover

George Papamokos, FORTH Biomedical Research Institute, discusses the cover art he created for the latest issue of Biophysical Journal.

In eykaryotic cells, DNA is packaged within the cell in a state called chromatin. Histones, the main building blocks of chromatin, are among the most highly conserved proteins of eukaryotes. Approximately 147 bp of DNA and an octamer of core histones constitute the nucleosome, the “core particle” of chromatin. The core histones form a globular structure but their N-terminal “tails,” which protrude from the core particle, are unstructured and are thought to fluctuate incessantly. The N-terminal tails can be chemically modified at specific amino acids in their sequence. Posttranslational modifications (PTMs) of histone proteins can either alter the chromatin structure or recruit specific domains of chromatin-associated proteins.

The cover art shows scales of biological matter and events observed on it: 1. the nucleosome core particle with protruding histone tails; 2. heterochromatin Protein 1 (HP1) bound to an H3 methylated oligopeptide, the prototype of PTM-mediated regulation of transcription; and 3. the interaction between residues of the H3 oligopeptide and HP1. The latter was observed after employing full atomistic MD on variably modified structures of HP1 bound to H3, while the former two are crystallographically determined structures.  Based on our results and experimental evidence we propose that the ⁷RKS¹⁰ motif is a tertiary functional switch of the H3 tail. Various intrinsically disordered proteins carry this motif as well.

The image was created by George Papamokos, after inspiring talks with Prof. Kaxiras and Prof. Politou. VMD and Adobe Photoshop were used. In the image, nucleosome DNA bps and its histones are displayed in paperchain and surf style, respectively.  Each histone dimer is represented in a different color.  HP1 chromodomain and H3 oligopeptide are displayed in new ribbons and surf style. In the atomic scale, the interacting residues are displayed in licorice style. Additionally, salt bridges are dotted.

We are very happy that our image was chosen for the cover art of Biophysical Journal.  Such exposure of our work gives us the opportunity to expand the network of collaborations and we are always open to such a challenge.  Furthermore, it gives us the chance to share a new point of view related to the debate of contemporary biology between those who translate PTMs of histones as a code and those who consider them as a daedal regulatory network: They may additionally be considered as a typical function of intrinsically disordered proteins.

Related work of the contributing labs can be found by interested readers following the links below:

http://www.seas.harvard.edu/ekaxiras/
http://www.bri.forth.gr/research_groups/georgatos.html
http://pc164.materials.uoi.gr/dpapageo/
http://www.bri.forth.gr/research_groups/politou.html

PDB accession codes of nucleosome and HP1-H3 complex:  1AOI and 1KNA

Dear Molly Cule: Negotiating a Postdoc’s Salary

Molly Cule is an Associate Professor in a medical school at a public university in the United States. Professor Cule is delighted to receive comments on her answers and (anonymized) questions at mollycule@biophysics.org, or visit her here on the BPS Blog.

Dear Molly Cule,
I’m about to finish my PhD and have been offered a postdoc position that I’m excited about. However, the PI won’t go above $38k for a salary. I recently got married and we’re expecting a child. Raising children is expensive and as somebody with a family I think I need more than what a single postdoc gets. What should I do?
–Poor, from Pennsylvania

Dear Poor,

Fixing a salary for a new postdoc can be a tricky process, both for the PI and the trainee. In the US, there is often some room for negotiation, although in other countries the system may be more rigid. Even in the US, the PI may be bound by institutional or department procedures. In my “administrative unit,” for example, PI’s are “encouraged” to pay at least 80% of the NIH scale, although some trainees make a lot more than this and some a little less.

One of the reasons fixing the initial salary can be difficult is that the PI and the potential postdoc often have different goals. The trainee is frequently trying to get the highest possible salary while the PI might be trying to pay the minimal amount required to recruit a new lab member. This is not necessarily because the faculty member is frugal (a polite word for mean). They could be trying to harbor their resources so that they can pay for a technician or a new piece of equipment to support the postdoc and help him or her to be successful.

There are many different strategies that you could adopt in your situation but my advice is to try and negotiate fairly and openly with your potential mentor. If the process goes well, there’s a good chance you’ll come to a reasonable compromise you’re both happy with. If, on the other hand, the negotiation is emotionally difficult and overly tense, you might want to think carefully about whether or not you really want to work closely with this person for the next few years. Remember also that they will be thinking the same thing. It takes two to tango!

When you negotiate, try not to fixate on a specific number. In the long run, your “relative” pay may be more important. For example, a $38k salary will go a lot further if your postdoc position is at the University of Nebraska than if you’re moving to Columbia University and have to live in or close to New York City. Some institutions will offer you low-cost health care while others may require that you pay more out of your own pocket. You may also be eligible for retirement packages at some institutions but not at others. Being new parents will almost certainly change your tax situation, too—consult an expert about this to make sure. Bear these things in mind because they can make a big difference in the long run. Recognize also that if you’re offered $38k and other postdocs in the department are averaging $36k, you are already ahead of the pack. (Salaries at public universities are often available online, so do some comparison shopping. Check http://www.collegiatetimes.com/databases/salaries or the websites for local newspapers etc. for the information.)

If you’re left behind the eight ball and really can’t agree on a number, try to be (politely) creative. Perhaps your PI can offer your spouse a part-time position, or you can negotiate a bonus if you get a grant or when you publish a second Nature paper! If nothing works, you may just have to walk away, recognizing that you’ve priced yourself out of your PI’s market.

Finally, let me comment on “postdocs with families deserve higher salaries.” I’ve heard this idea before and I have some sympathy with it. After all, you’ve been studying and training a long time and it’s a pity that you’re not being better rewarded (financially) for your advanced skills. Nevertheless, you knew that being a biophysicist was unlikely to win you a Wall Street salary when you got into this game. You therefore shouldn’t be surprised that you’re not yet a millionaire. Moreover, having a spouse and family was a personal choice and, in my opinion, it’s not appropriate to suggest that it should influence your salary. You would probably be upset if your potential mentor had discriminated against you and recruited a single postdoc who would “spend more time in the lab because he or she wouldn’t be distracted.” Paying you more than a single lab member is equally discriminating against them.

In summary, my advice is to negotiate reasonably and fairly with your potential mentor and try to come to a reasonable compromise. Walk away if you have to, but recognize that if you’ve walked away from three jobs in a row, you’ve probably overestimated your perceived value.

Good luck and best wishes.
–Molly

Find a Mentor, Be a Mentor with the BPS Mentor Board

Are you a biophysicist in need of a mentor, or want to volunteer to mentor a biophysicist? Check out the new Mentor Board, an online tool that connects Biophysical Society members all over the world looking for mentors with members looking to volunteer as mentors.

A mentor can be an invaluable resource no matter where you are in your career. When you sign up for Mentor Board, you can choose a mentor with experience in the challenges you’re facing on your career path, whether it’s finding a postdoc position, getting tenure, or balancing time between your work and your family. You’ll have the option of choosing a mentor in your scientific area, or in a related area for a broader perspective.

Mentoring other biophysicists is a rewarding and manageable way to give back to the scientific community. Whether you’re looking to volunteer an hour a week or an hour a year, you can still be a mentor. Mentor Board lets you select your own commitment level so that you can decide how much mentoring fits into your schedule.

Create a mentor or mentee profile on Mentor Board and start networking today! Visit the mentoring page of the Society website for more information.

What’s Happening on Capitol Hill? HEARINGS!

While Congress may not be passing much legislation these days, its members are busy fact finding and collecting information through congressional hearings.  While hearings are held year round, the spring is a particularly busy time on Capitol Hill as various committees in both the House and Senate educating themselves about various federal programs and the President’s budget request for the upcoming year.  To learn about the budget request, committee chairmen invite government officials and outside experts to the Capitol to share information about their programs.

A typical hearing usually starts with an opening statement by the Chairman of the Committee and the Ranking Member, oral testimony by the invited “witnesses,” and then a question and answer session during which each Congressman is given a specific amount of time to query the witnesses.  Often during the Q&A, members ask questions that reflect particular programs of interest to them.  For example, at a hearing focused on the National Institutes of Health, a Member who is particularly concerned about cancer may ask a question about how much money is spent on cancer research.  The witnesses answer questions on the spot if they can, and when they do not know the answer, let the Committee know that they will submit the answer after they have had a chance to research the issue for the official record of the hearing.

The majority of committee hearings is open to the public, and often are now webcast.  Individuals can watch the webcast live or after the hearing is over.

If you would like to see a hearing in action, the Senate posts a weekly calendar of hearings at http://www.senate.gov/pagelayout/committees/b_three_sections_with_teasers/committee_hearings.htm and the House posts a daily calendar of hearings at http://www.house.gov/ .  This week, the following hearings should be of particular interest to BPS members:

Wednesday, March 28, 10 AM
Proposed Budget Estimates for Fiscal Year 2013 for the National Institutes of Health
Senate Appropriations Subcommittee on the Departments of Labor, Health and Human Services, and Education, and Related Agencies

Thursday, March 29, 2012, 10 AM
Federally Funded Research: Examining Public Access and Scholarly Publication Interests
House Science,  Space and Technology Subcommittee on Investigations and Oversight

Watch the webcasts and leave a comment letting us know what you think!

Voltage-dependent loop-gating on the BiophysJ Cover

Authors Taekyung Kwon, Thaddeus Bargiello, Benoît Roux, Jeff Klauda, Andrew Harris, and Sunhwan Jo discuss the science behind the cover image of the latest issue of Biophysical Journal.

The cover image shows the structure of the open Cx26 hemichannel from the extracellular entrance following refinement of the crystal structure by all atom molecular dynamics simulation in an explicit membrane (ochre sticks). Hemichannels are a critical component of gap junctions, which are specialized molecular structures directly connecting the cytoplasm of two living cells.

The figure highlights the position of extensive van der Waals (limecolored spheres) and electrostatic networks (yellow sticks) that stabilize a portion of the pore lining region, the parahelix (red ribbons). This region of the channel poreundergoes a large conformational change to form a constriction that closes the channel in response to negative potentials by a process termed loop- or slow-gating. A significant feature, which is summarized in the image, is that the van der Waals network stabilizes the parahelix in each of the six individual subunits (ice blue ribbons) by interactions that are predominately restricted to individual subunits, whereas the interactions among charged residues extend across subunit boundaries to link the dynamic motions of the six component subunits. The electrostatic network likely contributes to the formation of the loop-gate voltage sensor; the extensive intersubunit interactions suggest that the loop-gating process occurs by a concerted mechanism. The interactions between these networks play an important role in mediating dynamic fluctuations observed in the open state in molecular dynamics simulations.

The long term objectives of our studies are to elucidate the molecular mechanism of voltage-dependent gating by defining the transition pathway that links open and closed states and how the two states are coupled by voltage. This goal requires knowledge of the structure and interactions that stabilize the two conformational endpoints, their conformational space and dynamics. Our current studies are focused on defining the closed state by experimental methods and to use this information to create and validate atomic models of the closed state. That the cover image closely corresponds to the Cx26 open channel is supported by our previous studies that demonstrated the close correspondence of I-V relations computed with grand canonical Monte Carlo Brownian dynamics to those determined experimentally (http://www.youtube.com/JGenPhysiol).

The image was created by Taekyung Kwon, the paper’s first author, using VMD software. We were very pleased that the image was chosen to appear on the cover and hope that it will increase the interest and exposure of our study to the readers of the Biophysical Journal. Our feeling is that atomic models of protein structures are inherently artistic and we were all impressed by the composition and quality of the image that Taekyung created. The image provides a succinct representation of the essential features of the Cx26 structure that were explored in the paper.

The atomic coordinates of the Cx26 structure refined by molecular dynamics simulation are available upon request and will be available for download from the Bargiello website: http://neuroscience.aecom.yu.edu/faculty/primary_faculty_pages/bargiello.html. Websites describing the research of other authors of the paper are:
Benoît Roux: http://thallium.bsd.uchicago.edu/RouxLab/
Jeff Klauda: http://terpconnect.umd.edu/~jbklauda/index.html
Andrew Harris: http://njms2.umdnj.edu/njmsweb/pharm_faculty/Harris.htm

FIRST: P&G’s Recruiting Conference

For those of you interested in industry, P&G’s Focusing on Industrial Recruitment of Scientific Talent (FIRST) Conference may be the conference for you! It’s a recruiting conference mainly aimed at African American, Hispanic and Native American doctoral and postdoctoral scientists from STEM disciplines. It’s a three-day, all-expenses-paid program for top early career scientists who are looking for a broad overview of research in industry as well as getting an opportunity to network and interact with P&G managers. Discussions will include what companies are looking for in a new employee as well as cultural and workforce diversity and future innovations.

This conference will be held on September 16-19, 2012. Attendance will be limited so applicants must have a doctoral degree or expect to receive one by September 2013. Applications are due by June 30, 2012.

–Susy Kohout, Early Careers Committee member

The running of the lectures stampedes to a triumphant end

My big day has come and now gone – I happily gave my first oral presentation at BPS.  I arrived about 20 minutes before the start and the friendly and competent technician took my computer and resolved a slight issue with recognition of the projector.  I hadn’t seen the chairmen previously in the conference nor been in contact since the last BPS I attended in 2010, so it was nice to say ‘hello.’  I greeted the other speakers and took my seat, attentive as ever with a few more anxious butterflies in my stomach than I anticipated.  As I jotted down notes, I continually glanced over the big bullet points I had already read a hundred times over the past few days.  Finally it was my turn, I was ready.  I knew I could trust my computer since I had run through the presentation half a dozen times the night before.  As I began the intro, bam, the screen freezes, no animation, no movie that I programmed.  Awesome.  I manage to fight off the cloud of panic that momentarily tries to block my mind.  It turns out to be a minor flaw, a quick escape and shift-F5 and I’m up and running with no further glitch.  I’m happy with how the presentation went and had a nice question from the audience.  Then it was over, the first one lined up and knocked down.

Now, there’s no more need to munch down a pretzel-dog before a 3 hour poster presentation.  No more running from room 29 to 20D, across the entire quarter-mile convention center, in the Olympic-time 4 minutes calculated between the start of the questions section and the end of the following.  No more free goodies from vendors, who themselves are busy picking out bright-eyed grad students from well-funded labs.  No more coffee until … the next Starbucks, probably the one conveniently at the airport entrance and next to the security point and again next to the departure gate.  But it will all return again in 11 short months, when we will all again be putting together our presentations and posters that are promising, but not quite what we had hoped when we put together the abstract in October.

See you in Philly!