Senior producer Veronica Vaquer on the making of BPS TV

Imagine being hired by a foreign government to produce their local news. You’d have to learn a little of the country’s language and quickly assess what’s interesting and new to the locals. What’s common knowledge? What are their concerns and priorities? How do they communicate? Put another way, how do you capture issues important to an audience you’ve just met? This is Veronica Vaquer’s specialty. She was the senior producer of Biophysical Society TV at this year’s Annual Meeting, and, working for WebsEdge, she has produced television programs and web clips for diverse conferences- for medical and scientific societies and for police chiefs and fire chiefs. “We become a news channel for the conference attendees,” wrote Vaquer, “Often news or video production is trying to reach John Q. Public – but that’s not our goal — we want to have a more elevated discussion … about the topics at the Meeting.”

To produce BPS TV, Veronica worked with a small crew- editor, cameraman, logistics person, and a former L.A. TV reporter who conducted the interviews during the meeting. Six weeks to 2 months before the conference, they traveled to universities to shoot footage highlighting relevant research centers and technology. The clips produced from these trips were broadcast on TVs around the Moscone Center during the meeting. After the meeting, the clips become tools for the universities to advertise their strengths to funding agencies and prospective students. Once at the meeting, Vaquer and her team produced interviews with scientists and, each day, a one-hour newscast covering interesting events at the conference. You might have seen the interviews happening by the entrance of the exhibition hall.

For Vaquer, producing Conference TV is an opportunity to help people and professional societies get exposure for their work and tell their stories. Before working for WebsEdge, Vaquer worked for 10 years in local news, where reporting is intended to be disinterested. Here, Vaquer enjoys being able to help attendees articulate their thoughts in compelling videos. That can mean, in our case, creating videos that celebrate crystallography or highlight a symposium. At many conferences, there is also a big concern simmering under the surface of the main business. Making a video with Professor Steven Block of Stanford revealed the depth of the research funding crisis to Vaquer. So she drew out the theme from different perspectives over the rest of the conference in videos now available to everyone online.

Next time you’re at a conference make sure to look your best, you never know when you might be on TV!


Restaurant-Style Review of Biophysical Society 2014

It’s been a while since I wrote a restaurant review and given all the great food I had in San Francisco, I’m inspired to present my final thoughts on this year’s meeting a la carte style….take what you like.

Science: The science was obviously the best part of the meeting. I enjoyed all the sessions I went to, though it was unfortunate that the East Coast storms prevented some of the speakers from attending the meeting. The big talks from Carlos Bustamante, Steven Chu, and the Award winners were all very interesting. The poster sessions were really well organized and made it easy to browse by your topic of interest.

Social: I was highly amused and slightly shocked at the post-National Lecture reception and dance. I guess those biophysics professors have got some moves! The ice cream and wine probably inspired people to rock out a little to live band as well. It was highly entertaining all around. The one thing I would like to see different next year is for the dinner meetups to start after the talks have concluded. I would have loved to go eat with some attendees but I wasn’t able to make it before the session ended. Some sort of lunch socializing (perhaps with a food order?) would have been awesome as well.

The Venue: I have always liked the Moscone Center area in terms of ease of transportation, nearby food, and the lovely Yerba Buena gardens right next door. I’m glad the meeting was held here and I hope everyone had a chance to explore the surroundings. Next year should be great as well with the Baltimore Convention Center sitting next to the fabulous inner harbor.

The Sides: I loved the Quartzy networking cards that made it really easy to keep track of the posters you visited and the people that you talked to. I will have to present next time just so I can get a few of my own. On the other hand, the phone app for the meeting could definitely use a few tweaks. The extra features, like the check-ins and messaging, were nice but the main purpose of the app is to make it easier to plan your day. It was a little user-unfriendly when it came to scheduling sessions or simply figuring out what room a talk was in.

Exhibit Hall: This part is probably a little biased because I got a good amount of swag (and candy!) from all the vendors. The photo contest and daily trivia were great add-ons as well, and I connected with plenty of aspiring people at the Graduate Institutions Fair. I wonder if there are plans to expand the variety of side activities for next year. It would be enjoyable to have a science communication contest of some sort such as the ever-growing three minute thesis competition.

Overall 5/5 Stars: It was a really good time and I enjoyed sharing it with all of you on the blog and via Twitter. I hope to do it again next year in Charm City!

Lessons from a career workshop

It’s taken me a few days to actually sit down and write about a career workshop that I attended on Monday. The conference schedule was so jam packed and rich that I’ve been running from one talk to another resting only to look at some posters and socialize with fellow students.

Stepping into Joe Tringali’s workshop, “Beyond the bench: preparing for your career transition in the life sciences”, I had expected to get a list of employment opportunities in the private sector – which I did get (more on that below). But more interestingly, I got a broader lesson in good old advertising from Tringali, a veteran employment firm owner in the New England area.

The key message of his workshop was: tailor and reinvent your professional image for the employment of choice.

While this statement is wildly abstract and has the ring of an age-old adage, it still contains grains of truth and deserves a moment of thought.

Tringali walked his audience through the logical and chronological flow in this tailoring process. The first step is to decide on a career path, arguably the most important and variable. Once this decision is made, Tringali offered some general advice and actions for crafting a professional image.

Show initiative in the field of employment

  • Joining professional associations
  • Taking related courses
  • Enrolling in a certification program
  • Even taking related unpaid projects.

Think from the employers’ point of view

  • Highlight only experiences relevant to the job post
  • Clearly state the reason for career shift
  • Emphasize your potential contribution to the position
  • Assure the employer of your interest in the company by conveying your depth of knowledge in the job position and company

Communicate your career interest to others

  •  Enunciate your career intents to references and recommenders
  • Talk to people currently in the careers of interest

Tringali also gave a list of PhD careers that are currently in high demand. You can imagine applying these broad guidelines of tailoring your professional image to any of these careers.

  • Regulatory Affairs
  • Medical Communication
  • Medical science liason
  • Sales/business development
  • Pharmacovigilance/drug safety
  • Project management
  • Tech transfer
  • Clinical operations

Distance Measurements by D.E.E.R. Workshop: Do Spin Labels Lie?

Dear Readers,

Crystallography (and increasingly, electron microscopy) can provide beautiful and detailed maps of proteins as well as other important macromolecules. What I’ve left out in my earlier discussion is the fact that these pictures only offer snapshots of the protein at various moments in time. Think Empire Strikes Back, where Han Solo is frozen in Carbonite, and remains stuck in a state of suspended animation for all time (or at least until Return of the Jedi). This is sort of like a crystal structure of a molecule.

Of course, all of the interesting things about a protein can be traced back to not only its structure but also its dynamics. A protein’s motion dictates how it functions as an enzyme, how it modulates structural changes, how it interacts with partners, and so on. There are certainly crystallographic methods aiming to capture the dynamic behavior of a protein (e.g. time-resolved studies, XFEL). Nevertheless, these techniques require a hardiness of crystals that isn’t always possible. There is a growing list of emerging biophysical techniques which can examine protein conformational changes. In fact, this meeting has had fascinating presentations about all of them. One technique that is regularly used in our group is Electron Paramagnetic Resonance Spectroscopy, which makes use of free radicals to probe protein motions. Since most proteins lack intrinsic free radicals, we introduce them by way of a covalent probe, known as a spin label. The free radical spin label then absorbs magnetic radiation depending upon its environment. This in turn can provide information about stable conformational changes made by the protein, depending on the placement of the label. Examples of this include changes made by transport proteins to facilitate substrate delivery (which I presented about) and domain motions within proteins during enzymatic activity.

While traditional EPR technique uses only one spin label to study protein motion, a few EPR techniques of burgeoning importance utilize multiple (usually two) spin labels to make distance measurements. This is based on the degree to which the free radicals interact. The information provided by these techniques is a distribution of possible distances of the labels from each other, from which we can infer how the protein behaves in different conditions.

Sounds great, right? An inherent error in all EPR measurements is the degree of rotational freedom these spin labels have (think of a tether on a cone). All small changes in distances thus come with this caveat: any change in signal you observe can be attributed simply to the spin label side chain motions. That limits the resolution of this technique, but still makes it a sensitive probe for conformational changes of 15-20 Angstroms for continuous wave techniques, and 20-80 Angstroms for pulsed techniques (like DEER, or double electron-electron resonance). Those measurements are extremely useful: in addition to providing information about protein dynamics, they are an excellent complement to crystallographic data, where proteins are often rigid and can adopt unnatural conformations. This allows for a more complete picture about how a protein actually functions.

Well, not so fast. Florida State’s Peter Fajer delivered a remarkable presentation to close Tuesday night’s workshop (Distance Measurements by D.E.E.R.) titled, “Do Spin Labels Lie?”. Using simulations, he demonstrated that the most commonly used spin label, MTSSL, experiences rotations of around 20 angstroms while attached to proteins. This doesn’t even include the protein’s backbone motions. The observation is pretty incredible, and calls into question years of measurements made by researchers in the field on a variety of systems. I’m certainly going to follow up on this work and reassess my data and interpretation. I’m amazed that this research was not done sooner, and kudos to Fajer and his group for looking into this phenomenon. His recommendation was to use shorter labels or bifunctional labels, which bind to two nearby cysteines and experience limited rotations. Fascinating. I now truly appreciate what “disruptive” means – this research is the embodiment of the word!



Biophysics in Industry: Some thoughts on the Amyris talk

As a Berkeley bioengineering undergraduate, I was imbued with the gospel of metabolic engineering. The potential to use self-replicating microorganisms to produce useful chemical and therapeutic compounds in an eco-friendly way has not only attracted vast government funding, but also venture capital to commercialize these biological processes. For me, the success story of synthetic artimisinin production from the Keasling lab at UC Berkeley was a shining example of the tangible impact scientific discovery can have on industry and society.

The current vice president of R&D programs, Tim Gardner, at Amyris, the company that first developed and optimized artimisinin production in genetically engineered yeast strains, gave an early morning talk Tuesday. I was both excited and curious to learn more about this company. Gardner presented a clear overview of the pipeline involved in selecting and optimizing yeast strains for production of the company’s current product, farnesene, a compound that can be converted to biofuels. Gardner highlighted that the R&D process uses much of the fundamental tools developed in academic research such as directed evolution and screening techniques. But the main difference is that these processes are mostly standardized and automated at Amyris. Gardner listed four broad principles that have facilitated the productivity of the company.

  • Standardization
  • Automation
  • Systematic storage and tracking
  • Quality control

Standardization of the “DNA parts” used to construct yeast strains lends the system to automation. Automation of the cloning process improves throughput of strain construction and screening. Careful tracking and storage of information in databases enables more efficient tracking and communication of information. And lastly, rigorous quality control helps to ensure reliability of results.

Gardner moreover made an interesting point about reproducibility of results in the development pipeline, saying that the limitation to programming cells is not the ability to manipulate DNA but the ability to make accurate measurements. Gardner’s points on standardization and automation seemed like the bread and butter protocols for many industries, but his comment on the nature of engineering microorganisms was more particular to the biological enterprise. Unlike traditional industries, the metabolic engineering companies rely on performance metrics that are inherently noisier due to biological and technical errors. To emphasize his point, Gardner told an anecdote about increasing farnesene yield. A reduction in the measurement error from 2.3% to 0.5% made a dramatic difference in production because it revealed the location in the development pipeline that required optimization and this revelation resulted in an increase in both reproducibility and the yield of farnesene.

Having previously been an academic who authored one of the seminal papers in the field of synthetic biology, Gardner keenly noted that industry has a more ascetic tolerance for error than academia. For example, a relatively small error in data collection is generally acceptable in academia, but might not make the cut in industry. Gardner attributes the irreproducibility of experiments some times observed in the biological literature to the lack of precision in measurements. While the amount of precision required in an experiment is dependent on various factors such as the signal to noise ratio of the experiment, the uncertainty in measurements clearly obscures the ability to extract more nuanced determinants of a biological phenomenon, and thus lead to irreproducibility of experiment when performed different environments. This brings up the question of whether there should be greater emphasis in academia for tighter error bars to improve the reproducibility of biological research. The title of the symposium was “Biophysics in Industry”, and highlights the impact of biological research on the biotech industry. But perhaps there is also something academia can learn from industry.


Job search advice from biotech industry experts

Monica Weil and Joe Tringali started working in biotech before it was “cool.” After sharing their wisdom at the Annual Meeting’s career Q&A session on Monday, they kindly sat down with me to describe their experience and advice for people interested in biotech or pharmaceutical careers.

The first piece of advice Joe gave was, “I wouldn’t be your own worst enemy, don’t screen yourself out.” In the job market, a company won’t necessarily find candidates with every item in their job posting, or “wish list” as Monica called it. Furthermore, one’s application might be a great match for an upcoming job opening that hasn’t been made public yet. Rejecting oneself may initially be easier on the ego than letting others do it, but Joe and Monica lay out a different, more robust ideal for the perfectionist in you- instead of striving to be the candidate who never fails, strive to be the candidate who mobilizes their resources and looks for creative solutions.

If one wants to do scientific research in industry, start by doing thorough research on industry. Joe suggests reaching out to people online and asking “I’m thinking about doing what you’ve done. What did you like about it? What didn’t you like about it?” Monica emphasized that industry isn’t “academia with more money,” it’s a different world with different rules, expectations and a different ways of life. Technical skills are transferable, but the image of a researcher toiling over their own science for years in the pursuit of  knowledge doesn’t apply. Instead, researchers who might enjoy industry (and successfully find a job!)

  • are excited about pursuing “knowledge so that…” as much as “knowledge for knowledge’s sake.”
  • have an interest and skill in collaboration.
  • are flexible and welcome change. (Projects change quickly and can simply get scrapped.)

A word of advice, Joe said at the end of our interview, “open your mind to all possibilities” don’t just get stuck in a path and keep pursuing it. Indeed, serendipity and openness to new possibilities are what brought Monica and Joe into biotech and pharma careers that they clearly love. “I wish I had a master plan,” Joe said, “but there’s no place I’d rather be.”

– A. I. Gilson


The next 100 years of crystallography: retroactively crowdsourcing the PDB

Dear Readers,

Macromolecular crystallography is my favorite scientific technique, and likely the most important one of the past 100 years. So many important discoveries are the fruits of this technique: the structure of DNA, the structure of the ribose, structural enzymology, the mechanism of muscle fiber contraction, and….I could keep going on. This topic has already been discussed in great detail, and will continue to be this year, the 100th birthday of X-ray Crystallography.

X-ray crystallography is certainly deserving of all of these accolades, and perhaps it is poetic justice that the next 100 years could mark its end, or at least as we know it. So was Gregory Petsko’s proclamation during his fantastic talk at the end of Sunday evening’s session (Symposium: Celebrating 100 Years of Crystallography), and I couldn’t agree more. Petsko exclaimed, “It needs to end!”, and I found myself nodding along. At its surface, crystallography is a beautiful technique: the specimens look gorgeous, the diffraction patterns can cause grown men to weep, and protein structures are delightful to look at. A more detailed examination reveals a technique wrought with clumsy: growing crystals is nearly a random exercise; the crystals themselves are unnatural environments for proteins, forcing them into strict conformations; looping the crystals out of their drops is unwieldy, and even the most experienced hand can lose a crystal; cryoprotection is frequently a haphazard endeavor; and radiation damage can effect the amount of data you can collect – better have more than one crystal! So, Petsko says, we really need something better.

So what’s better? The X-ray free electron laser – like the SLAC nearby – is a new and exciting technology that is just starting to yield interesting results (John Spence: XFELS for Imaging Molecular Dynamics). As Spence discussed, the bottleneck of growing large crystals (a nontrivial process) may soon fade, as this technology makes use of much smaller crystals. (Frequently, protein crystallographers will start out with small crystals that need to be optimized to larger crystals for conventional X-ray crystallography. XFEL obviates this step.) Check out the new GPCR paper published last month in Nature by Cherezov et al. Their methodology also eliminates the need to handle crystals, as one can simply pass the medium that facilitates crystal growth in front of the pulsed X-rays produced by the XFEL (William Weis also had a great summary of the technical advances that facilitated the GPCR work during Sunday’s X-ray session.)

Eventually, Spence says, the promise of a prediction in a paper published nearly 15 years ago (Neutze et al, Nature, 2000) will come to fruition, and single-molecule diffraction will be a real thing. This breakthrough, coupled with ever-increasing computational power and the development of new phasing techniques, will make structure determination a trivial exercise; if you can get a stable molecule, you’ll be able to solve its structure, and the PDB will contain structures of perhaps every relevant protein known to humans.

Sounds like a big data problem! Atul Butte’s fantastic seminar on the big data problem in science (Symposium: Biophysics of Personalized Medicine) can be applied to protein crystallography. He pointed out that hundreds of thousands of hard-won data points exist in a free, publicly available database of microarray data, begging to be analyzed. His group has been working to make sense of this huge repository, which could lead to exciting new therapeutic approaches. (Butte calls this “retroactive crowdsourcing”.) Something similar may soon come to the fore in the protein world, as Petsko discussed. There are nearly one hundred thousand crystal structures freely available in the Protein Data Bank, with tremendous redundancy. What do we do with all of this data? Can we say something about the prevalence of certain folds? (Via Petsko: 56 protein folds represent 50% of all structures. Amazing.) What sort of evolutionary relationships can we deduce from this? Can this be used in a translational manner? There is no limit to the questions that we can ask here, if we simply have a way to consider all of this data at once. The PDB itself must have colossal value; Spence mentioned anecdotally that a carat of protein crystals is 12,000 times more valuable than a carat of diamonds (also during the X-rays session). I can readily believe this, given the materials’ costs, labor, and time it takes to get protein structures. And it’s all out there for free. I love science.

Back to big data: this isn’t just another buzzword; based on the seminars presented here at the BPS Annual Meeting, it is the present and future of biology. I think Gregory Petsko’s insight is extremely helpful for graduate students looking ahead to career opportunities: in the coming years, it won’t be useful to simply call yourself a structural biologist or a crystallographer; the techniques are increasingly accessible to researchers and don’t require years of training. Gone are the days when you can simply hang a shingle saying “Protein Crystallographer” on your door and ply your trade. Petsko says we need to be biologists again first and foremost, which is a good lesson for someone such as myself, who often focuses on the structures and gets lost in detailed discussions about the biology.

Until later,