Lots of Mechanobiology and Cell Mechanics @ BPS

There were a a lot of talks and posters on this session and I obviously cant cover all of them, but here are a few highlights!

The Mechanobiology subgroup is growing over the years.
It ranged from cell clusters to single cells, from engineering techniques to mathematical modeling and more… It was an action packed day and here are some of the highlights.

Vinculin catch bond is directional! Alex Dunn’s lab has now done neat experiments to show that Vinculin forms a catch bond very neatly in the direction of actin flow. This allows the binding to the rearward flowing actin and slowing it down.

Another neat talk by Kristian Franze (who is also the president elect for 2018 – Congratulations ☺) showed their interesting work on how neurons migrate through repellant gradients. They show that during development, when neurons enervate the area of the brain, they do so even though there is a chemical repellant present there. Using both imaging and biophysical manipulations invitro and invivo (AFM cantilever) they show that the neurons require a particular range stiffness to migrate and reach their final destination. This led to interesting speculations about the reason for poor neuronal regeneration in scar tissue in the brain, which is actually stiffened by the glial cells.

There were two talks talking answering questions of cell division – one dealing with kinetochores in chromosome segregation and another about the acto-myosin contractile ring. Mary Elting’s work answered questions about where are the spindles anchored or rather where are the K fibers, just at the tip or throughout the entire spindle during chromosome segregation? They used Ptk2 cells – as these cells have very few chromosomes hence easier to work with. She cut the spindles at different distances from the chromosome and measured chromosome recoil. These experiments suggest that the K fibers are anchored almost throughout the length of the spindle.

Binh An Truong Quang from Ewa Paluch’s lab, took to the theme of acto-myosin ring contraction. The major question was how does the ring contract. Using double-labeled myosin they devised a nice way to measure the angle of myosin with respect to actin. They show that as the tension in the ring increases about 2 fold during contraction, they myosin angle changes with respect to the actin, explaining the increase in tension.

Lisa Manning gave a great talk no their modeling studies, where the magic number was 3.81. What is 3.81, that’s the ratio of perimeter:square root of area (model parameter). Of densely packed cells. What does this tell us, that by just measuring these parameters, one can actually tell if the cells are stationary or fluid like. This was an interesting problem from the physics perspective as cells have no gaps so how can they flow – by interacting with their neighbours and it turns out that these interactions can change the model parameter. Hence just by looking at the value of the model parameter one can easily determine the state of cells. Further, she had developed a very a neat phase diagram where cell shapes were determined as a function of stiffness and what would happen in a cell sheet.
Otter Campas has developed a very nice method to forces in an intact tissue. They use magnetized oil droplets roughly 3 times the size of the cell and insert it in the tissue (they were focusing on developing zebra fish). Using this they can apply pair forces to the cells and measure local strain maps without perturbing morphogenetic movements.
Switching gears here, I went to attend Miriam Goodman’s talk, as I would be co-chairing the session with her the next day. It was amazing, where they set out to understand how worms respond to touch. The assay they use is to poke the worm with an eyebrow hair. They show that the force generated by this, though variable between humans – is enough to saturate the response of the worm (2pN). This is primarily mediated by MEC4 (ENAC Channel proteins). Worms expressed these channels in the epidermis near the skin and those lacking these channels are touch dead. Further, they can make stiff (using glue) or soft worms (dissecting the gut) and measure how the touch response is modulated.
Great! That was Saturday, a relatively short day as it ended by 6pm.. And then it was Mardi Gras festivities. Ofcourse the political satire themed parade was on everyone’s agenda! What Can I say it was fun! Lots of people wrote about that, but here is what I found – A monument on the banks of Mississippi to guess what? That’s right! Immigrants! Woah!

Enjoy the big and easy 🙂

Rishita Changede

Failing to prepare…

Benjamin Franklin once said, “By failing to prepare, you are preparing to fail”.

Ok so that sounds frightening, but in my opinion, Ben was on the right track with that one. Even if things don’t always go as planned, having a plan in place keeps me grounded and motivated. I am a big believer in planning ahead– one of many reasons why me and Ben Franklin are very alike and if he was alive right now I am confident we would be great friends.

This morning I had the pleasure of attending the Career Center Workshop on selling yourself to the life sciences industry. When I read the title of this session I was not a fan of the idea of “selling” myself, but in the interest of getting some career advice, I elected to attend. I am so glad I did!! This session was run by Joe Tringali (who totally rules by the way) and was an hour full of helpful tips and tricks. Joe’s prepared material for this session was fantastic, and he also did a great job of engaging attendees of the session and making sure everyone’s questions were addressed. So without further ado, here are my take-away points from this Workshop!

  1. Know the difference between a resume and a CV— and when using each of these is appropriate!!  Joe emphasized that CV’s are best when talking to scientists, but for a lot of large companies, HR reps will be reviewing applications so a resume may be a better choice. Also, resumes should be concise and should very obviously highlight which techniques and skills you possess, plainly identifying what qualifies you for the position you’ve applied for.
  2. Target your message! Do not be ambiguous when it comes to your cover letter. Employers should not look at your application and think that you are tossing in a resume with their company just for the heck of it. Indicate that you have done your homework and are interested in the position for X reasons, you love the city of Y, and you have Z qualifications, therefore are a great fit.
  3. Reach out using non-traditional methods if the traditional job search is not going well. If you’ve applied to 100 jobs via Indeed and Monster, and no one is answering you, try a different strategy!! If you can identify someone within the company you are interested in using LinkedIn, and you know you are qualified to join their group, try sending out them a short email with your CV/Resume attached, and asking if they may be able to circulate it for you. Worst case scenario, you are back where you started (jobless with no prospects). Best case scenario, maybe they have an opening! Or if they don’t, maybe they know of an opening you would be a good fit for! Bottom line is that networking is important, and dropping someone a line is rarely a bad idea so long as you are being respectful and not creepy…. Emphasis on the not creepy part.
  4. Make sure you and your references are on the same page. Okay so this was something I did not know going in– Joe says that checking references for industry jobs is generally kind of an afterthought. But nevertheless, it is important that anyone you have listed as a reference is actually going to talk you up. If you have a boss/PI that doesn’t want you to leave the company/lab, it’s still okay to use them as a reference, but make sure the interviewer knows the situation. Your best bet is to list references you know will say you are totally fabulous. It is important to prepare them for incoming calls, so they don’t say “ah yes Sally has always wanted to live in Tokyo” when the interviewer is calling about a job you’ve applied for in Boise, Idaho.
  5. Don’t talk about money right off the bat. Joe says that employees will be payed an appropriate, fair wage based on their qualifications, the wages of their colleagues, the cost of living in the city they’ll be in, and whether they look like Angelina Jolie. I made that last one up- he did not say you need to look like Angie, but the rest of that is true. So don’t stress about the dollar bills! It will more than likely put employers off if you start trying to push them into giving you loads of money before you’ve even finished the interview process.

Thank you to Joe Tringali for the great workshop this morning, much appreciated!! Also Happy Valentine’s Day to all of you blog readers!! I’ve got my ion you ❤

Cheers,

Ellen Avery

Intrinsically Disordered

As a first year graduate student, I felt a sense of camaraderie with intrinsically disordered proteins. The fact that these proteins did not fit into one structure resonated with me. Perhaps you can relate. As a back story, I had just switched from performing optogenetics research in my undergraduate work to studying the biophysics of proteins. Looking back five years later, I am amazed at how much this field has grown, as have I.

For me, this year the talks at the IDP subgroup and through the IDP symposiums were the most exciting. Who knew that even PKA has intrinsically disordered residues important in signalling! And the role of disordered proteins in circadian rhythms help me to make sense of and cope with jet lag. Moreover, as a MD simulations researcher, the talks on the accuracy of force fields for IDPs and structured proteins made me very excited for the future possibilities of simulating IDPs.

I think one of the best things I did in my graduate work was to become part of the IDP subgroup and run for graduate representative. I have collaborated with graduate students and postdoctoral scholars in the field of IDPs to write up a newsletter each month; “The IDP State Letter.” In this newsletter, we would summarize and read various new and old papers in the IDP field. This newsletter forced me to write and read science that was at times quite tangential to my own research. There were times when I felt that I had too many important things to do in the lab and could not contribute. But instead, I paused and took time away from my research to read something completely unrelated to my field, which somehow always helped me to see my own research through a new lens.

As a newly minted postdoc, I encourage everyone to take part in this sort of “extracurricular” education, many of which are possible through the Biophysical Society. It has helped me to realize my passion not just for science, but for communicating science.

If you are interested in staying up to date on the newest and most notable research in the IDP field, check out the IDP state letter by enrolling in our mailing list here. If you would like to branch out of your normal day to day and contribute to the IDP state letter, feel free to email me!

JMS

schiff.jamie@gmail.com

The Battle of the Oysters

BPS17 is slowly coming to a close, and while the science has been great and exciting so far, the food scene has been even better! Before coming, I had a list of food I knew I had to try down here: beignets, char-grilled oysters, crawfish étouffée, hush puppies, jambalaya, muffalettas, hurricanes (not technically food, but still), etc. I’m happy to say, that I have tried all of them since Friday. I actually think by the end of the day Saturday I tried them all. Every day thus far, I’ve had some form of oysters (mostly some form of charred oysters). With only a day left of BPS, I wanted to inform all of you where I’ve had oysters, along with the experience of getting them. I’m a self-described food connoisseur (my friends and my mom agree), so my advice is pretty trustworthy.

Friday Night

After landing and finding my hotel, I went to the French Quarter and met up with Alfredo Caro and his friend, Mariano Dellarole, who were already at Felix’s Restaurant and Oyster Bar. When I sat down, Alfredo said that they had already ordered a dozen char-grilled oysters. I replied with an ecstatic, “Awesome!” However, deep down inside, I was not excited. The first and only other time I had oysters was in Virginia Beach in high school. I remember picking out oysters Rockefeller, since I loved seafood and thought that I’d naturally enjoy them. I also remember tasting them, immediately regretting getting them, and remembered every other poor choice I made in life. Suffice to say, I was not looking forward to the oysters. However, my friends back home in Philly know that my stance on food is, “Yes!” So, in order to not seem rude and to not break my own code, I decided to just try one. When they came out, all 12 oysters were arranged around a large chunk of bread, swimming in a sea of butter (pictured above). I picked the oyster closest to me to try. And that oyster changed my life. I believe in oysters now. That oyster was delicious, juicy, and exquisite. I’d love to go into more descriptions of how it tasted, but I just can’t. No description could ever give that oyster justice. I never even knew I could love oysters that much. I had three more by the way, each one just as beautiful as the first. But that first oyster will always be special to me. I also ended up getting blackened redfish with crawfish étouffée as well. Also delicious, but that oyster will forever be king.

Saturday Lunch

Before my subgroup session started, I bumped into two other students from my department, Michael Woody and Betsy McIntosh. We waltzed over to Galliano Restaurant, a Cajun eatery not too far from the Convention Center. I was pretty hungry, since all I had to eat so far that day were beignets and a few sips of café au lait (from Café du Monde, and yes, they were delicious. I also am in love with beignets, but remember, this post is about oysters, so let’s stay focused!). After we got our menus, guess what the first thing I saw on the menu was (after the first four pages of drinks)? Oysters. Char-grilled oysters. Let’s be honest. I still had that oyster from Felix’s on my mind, so I wanted to get some more. Our waiter first brought out hush puppies which were devoured within a couple minutes by our table. Finally, my oysters came out, beautifully arranged on a bed of salt, with bread and lemon slices in the center. The oysters were topped with the Chef’s Special Sauce. I don’t have a clue what was in the sauce, but it is quite tasty. A few splashes of Louisiana Hot Sauce made it even better. Overall, these oysters were also delicious.

Sunday Dinner

After another full day of science, I went out to dinner with Betsy and my friend Mara Olenick (also from my department), who had been sick since she landed in New Orleans. She’d really eaten only crackers for the first few days, so she was looking forward to having real food. We went to Mulate’s for dinner, where every night at 7 PM, they have live zydeco music. I decided to order Cajun smoked oysters along with crawfish étouffée. The oysters were shucked and sautéed in cayenne garlic parmesan butter. It was good, but I actually preferred the crawfish étouffée over the oysters. I also got to try some of Betsy’s stuffed crab platter, which was also very delicious.

Monday Dinner

Monday night, before the National Lecture, Mara and I went to Drago’s Seafood Restaurant. Earlier this month, the co-founder, Drago Cvitanovich, passed away at the age of 94, who was beloved by the community. Drago’s is famous for its charbroiled oysters, known as the “Single Best Bite of Food in New Orleans.” I was contemplating between ordering a half dozen or a dozen oysters, but Mara told me to follow my heart, so I ordered the dozen. I also ordered a side of red beans and rice, which is apparently a local custom to eat on Mondays. When our waiter brought out the oysters, I instantly was reminded about my time at Felix’s. These oysters too were swimming in a sea of butter, with two huge chunks of bread on the side you could use for dipping into the butter once you were done. These oysters were almost as good as the ones at Felix’s. Overall, I was very delighted with the charbroiled oysters, and doubly thankful for ordering a dozen rather than just a half dozen.

So, four oyster feasts in, I can say I’ve had a great tasting of different oysters. However, if you only have time for one oyster feast, I would highly recommend Felix’s. It’s out in the French Quarter, but it is worth the hike. It isn’t too crowded, prices are great, and it’s where I learned to believe in oysters. Maybe I’m just biased, but we all know the saying, “You will always remember your first love.” I agree, just except in this case, your first love for an oyster.

Also, I just wanted to take the time to wish my mom a Happy Valentine’s Day, who has been reading my blog posts every day!

Take it easy in the Big Easy,

Martin

The Traveling Biophysicist

I struggle with good planning during conference meetings. We are only in a host city for a limited amount of time, and we are expected to not only engage in meaningful scientific discussion but also explore the surrounding community. This is my third time at a Biophysical Society Annual Meeting, and I do not yet have a solution.

As a simulationist, I of course find a good comparison between this problem and the one of the traveling salesperson. The traveling salesperson is the story of some unfortunate individual who, starting from home, is expected to go between a number of cities spaced out in a certain geometry and visit each city only once (hopefully making a sale) before returning home. This is directly relatable to our experience as conference attendees. Starting from the Ernest N. Morial Conference Center (or your hotel if you wish), you must not only work to your way to all posters, platform sessions, and symposia you’re interested in but also find your way to the most popular tourist destinations: Bourbon Street, Café du Monde, the Mercedes-Benz Superdome—how can you possibly manage this?

The problem presented by the traveling salesperson is one of note to computational scientists. It’s in the class of NP-complete problems, meaning that (in colloquial terms) this problem is very, very difficult and takes a lot of time to solve. Protein folding is another example of an NP-complete problem. To my students, I like to present a naïve (and classical) brute-force algorithm to fold proteins illustrating this point. You presume that you have a protein 100 amino acids in length, and you take the backbone phi and psi angles as the only interesting structural feature of this protein. Very ignorantly, you assume that each phi and psi angle can only adopt 3 possible conformations (a quite dramatic simplification). Excluding one phi and one psi angle from the termini, you can say that the protein therefore can adopt 3198 conformations. If your (somewhat old) computer takes 0.33×10-9 seconds to sample a single conformation, then you are expecting 2.8×1096 years of simulation time to go through all possible conformations. This is a very long time (much longer than the age of the current universe) and is therefore unthinkable to address computationally.

As biophysicists, we know that protein folding does not occur in a brute-force manner. Levinthal’s paradox, in a few words, stipulates that protein folding must be a directed and nonrandom process. In reality, proteins fold along a pathway driven by energetic and entropic demands. Likewise, there must be a way to direct our exploration of conformational space within the city of New Orleans—how can we minimize our travel along our trajectory through the city?

Despite the scientist in me wanting to construct an energetic function that considers my position and affinity to proximal points of interest, I know that I will not solve this problem during this year’s meeting. As the only alternative, I am more inclined to follow the fate of the randomly folding peptide, often at times making arbitrary choices out of sheer convenience. Yet, the desire within me remains to optimize my time and achieve true efficiency. Maybe next year.

Chris Lockhart

Producing reliable science

Have you guys recovered from the national lecture yet? I definitely haven’t!

I use the phrase “recover” for a reason. What struck me in the lecture was this realization: we never study cells in their native environment!

It struck me for two reasons. One, it’s scary. Second, how come we never thought of it? We know it from our undergrad years that when you strike an object with a photon, you perturb it. When you perturb something, it is no longer in its native state. It’s really that simple, yet it took me all these years to realize that. And scary because….well……in the words of the speaker himself, “seeing is believing, but how can I believe what I see?”

Producing reliable science was the theme at most of the sessions I attended today. The ones I enjoyed the most were talks about development of force field parameters for molecular dynamics simulation. Force field parameters govern the strength of various interactions between atoms in a simulation, which in turn has significant effects on what we see in the simulation. Force field parameters need to be accurate to reproduce experimental data, and an enormous amount of effort is spent to improve this accuracy.

The first talk of the “Molecular Dynamics I” platform was by Paul Robustelli, from the David Shaw Research group. This group developed and maintains Anton, the most powerful supercomputer dedicated to molecular dynamics simulation. The talk focused on one drawback of the existing force field: no single parameter set accurately describes both ordered and disordered states of proteins. The Shaw Research group is solving this issue by modifying the way dispersion interactions are defined (for the mathematically inclined: we are talking about modifications to Lennard-Jones potential). With the power of Anton, their team has verified the new parameters on 20 different proteins.

The next talk, by Sarah Rauscher, described similar improvements to the CHARMM force field. CHARMM is one of the most widely used force field among biophysicists (our group included). CHARMM’s latest version, CHARMM36, had been showing something unexpected: it was favoring left-handed helices much more than what was observed experimentally. Dr. Rauscher described how their group went on to find out the source of the problem, and the results they obtained after fixing the same. The new CHARMM36m force field has much better agreement with the experimental structures, and has taken us a step ahead towards believing what we see.

Before signing off, I would like to remind you: I am presenting my poster tomorrow at poster board B536. If you want to know about exploiting tumor acidity for treating cancer and/or implicit solvent simulation of peptides to study helix-coil transitions, feel free to drop by.

7 Things To Do In New Orleans Before You Leave: A Biophysicist’s Guide

We find ourselves immersed in New Orleans, Louisiana, an old city with an abundance of history. As our time remaining at the Biophysical Society Annual Meeting 2017 dwindles, it’s important to ask ourselves what local experiences we’ve missed. Maybe it’s just me, but as a tourist I have an eternal struggle to find authentic experiences. But according to the Atlantic, authentic experiences don’t exist. Among many reasons, they cite the “traveler quantum effect” in causing this: because we are tourists, the mere fact of our being results in inauthenticity. Once we accept this, we can shrug off any doubts about experiencing “true” New Orleans, and we can focus on simply having fun. Here’s a list of 7 arguably “fun” activities to do after a day at the convention center.

1. Walk Along the Mississippi River
The Ernest N. Morial Convention Center is situated right next to the Outlet Collection at Riverwalk. When you’re done with the day’s sessions, enter the mall and continue walking north until you exit the mall again. Continue north along the choppy waters of the Mississippi. Along the way, you’ll be pleasantly serenaded by street music and will eventually find the Steamboat Natchez (which offers a dinner jazz cruise). Once you see Jackson Square on your left, stop.

2. Beignets at Café du Monde
You’re at the river. Before crossing Decatur Street to get to Jackson Square, you’ll find Café du Monde. This locale is known for its beignets and café au lait. Sadly, I attempted to visit the café Sunday morning but was beset by an incredibly long line. If you brave the wait, when you receive your beignet, you can ponder about the ratio of sugar to bread. How much is enough? Hopefully the answer you’ll find is similar to the answer I arrived at during previous visits to New Orleans: there is never enough. If you’re besmitten by the beignets, you can even buy the mix for home use!

3. Pirate Alley
After crossing Decatur Street and making your way through Jackson Square, you should turn left at the cathedral and then immediately right into Pirate Alley. I won’t distract you with the historical details, but this quaint alley is also one of the most allegedly haunted in New Orleans. As you walk through the alley and contemplate the existence of ghosts, be sure to stop at Pirates Alley Café.

4. See the Dueling Pianists at Pat O’Brien’s
Once through Pirate Alley, turn left onto Royal Street and then right onto St. Peter Street. On the left you’ll find Pat O’Brien’s, known for their dueling pianos and hurricane cocktail. Sunday evening I found myself at Pat O’Brien’s and quickly lost myself in the music. As one of the pianists belted out the lyric to the Eagles’ song “Hotel California” that “you can check out any time you like, but you can never leave”, I checked my watch and realized that too much time had passed. Beware: Pat O’Brien’s resists the flow of time.

5. Preservation Hall Jazz Band
Once sufficiently sated by piano renditions of the golden oldies, you can walk just up St. Peter Street to the Preservation Hall. Every evening at 8pm, 9pm, and 10pm they put on a performance featuring the world-renowned Preservation Hall Jazz Band. Tickets cost $15 per person and are first-come first-served (you must wait in line before the performance). The music is boisterous jazz from another era that shouldn’t be missed. If you have time, I definitely recommend going.

6. Lafitte’s Blacksmith Shop Bar
Once you exit Preservation Hall, continue up St. Peters Street and then turn right on Bourbon Street. Walk 3 or 4 blocks and then you’ll find Lafitte’s Blacksmith Shop Bar on the left. This bar is quite old (built between 1722 and 1732) and is claimed to be the oldest bar in the United States. Interestingly, the bar is lit by candles, which give it a very mellow atmosphere.

7. Frenchman Street
After Lafitte’s, continue along Bourbon Street until it becomes Pauger Street and then take a right on Dauphine Street. You’ll walk two blocks and then be on Frenchman, which is acclaimed for its jazz and nightlife. I will leave you to explore on your own here. When you’re done, order an Uber back to your hotel rather than taking the long walk back. Why not?

You will notice that this route avoids the heart of Bourbon Street. If you want to subject yourself to Bourbon Street crowds (see my previous post), I recommend stopping by the Musical Legends Park with its jazz at night. There is also a cocktail bar called the 21st Amendment—my favorite bar in the city—just off Bourbon Street on Iberville Street that has good late night jazz. If you have some time in the morning, I recommend trying brunch at the Court of Two Sisters, which operates from 9am-3pm. Finally, if you wish to mobilize yourself, I recommend taking a ride on the streetcar through the Garden District and appreciating the gorgeous buildings you’ll see along the way.

Chris Lockhart