Neurons, Brains, and Biophysics at the U.S.’s largest science fair

15,500 pipe cleaners.

160 showings of The Human Brain:  Images to Atoms

6000 individuals at the BPS exhibit booth.

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BPS Council member Bob Nakamoto, University of Virginia, helps elementary school students with their neuron models.

In a nutshell, these numbers wrap of the Biophysical Society’s participation in the 4th Annual USA Science and Engineering Festival held in Washington, DC, April 15-17, 2016.

In three short days, Biophysical staff and member volunteers gave over 6000 individuals a glimpse of the power and beauty of biophysics research through a short planetarium style movie showcasing images of neurons and proteins in the brain, as well as a hands on activity– making neuron models out of pipe cleaners.  Pretty amazing numbers considering the Society’s booth was one of over 1000 exhibitors at the Festival.

With a booth at the entrance of one of the exhibit floors (Yes, there was more than one at the festival!), the Biophysical Society’s exhibit was bumping throughout the entire event.  On Friday, school groups made up the majority of attendees, while on the weekend, the attendees were primarily families.  An estimated 345,000 people attended the free event, and it was very heartening to see the interest in science from the diverse crowd.

The Society would like to thank its member volunteers for showing up, being amazing educators, and sharing their passion for science with the next generation.  The Society would  also like to thank its partners in bringing the Dome to the event:  Wah Chiu and Matt Doherty, from Baylor College of Medicine, and the Houston Museum of Science for the use of their equipment.

Want to make a neuron model out of pipe cleaners at home or at a local outreach event?  Here are the instructions on How To Make a Neuron Model.

 

 

The Secrets of Fertile Gamete

April 24-30, 2016 has been designated National Infertility Awareness Week by RESOLVE, the National Infertility Association.  Basic research plays an important role in our understanding of infertility.  Here, BPS member Polina Lishko, Department of Molecular and Cell Biology
University of California, Berkeley,  shares information about her research on male infertility, what makes human sperm fertile, and the path that brought her to use her biophysics background in the field of reproductive biology.  

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Infertility constitutes a global problem, with male infertility contributing to half of all cases. About 80% of male infertility cases are considered idiopathic, which means we don’t know the cause. The only available treatment in such cases is limited to assisted reproductive technologies. This huge gap in our understanding of etiology of male infertility is partially attributed to our insufficient knowledge of physiology of human sperm cells. Frankly, we still do not fully understand sophisticated machinery that regulates human sperm motility and their fertilizing potential. Sperm cells or spermatozoa as we call them, are diverse and species specific not only in their morphology or overall appearance, but also in their choice of molecular mechanisms that drive fertility. Essentially, what works for mouse or sea urchin sperm, may not necessarily work for human spermatozoa. This is why our lab and other reproductive biology laboratories embark on the comprehensive study to define what makes human sperm fertile. Our ultimate goal is either decrease sperm fertility by developing novel contraceptives or increase sperm fertilizing potential to help infertile couples to conceive. But the first step in this task- is to define what makes human sperm fertile and what impacts this ability. Once one knows all major regulatory units of human sperm cell, one can develop a comprehensive diagnostic test that could help men test their fertility potential. This knowledge also will be helpful to develop novel contraceptives for both men and women, and ultimately, this knowledge will be vital to help infertile couples.

My scientific journey into reproductive biology was not straightforward. I was trained as biophysicist and neuroscientist and has spent significant portion of the graduate and postdoctoral research studying how ion channels regulate excitability of neurons, as well as studying molecular mechanisms of vision and pain. However, ion channels are important regulatory switches in many different cell types, and they have long been suspected to play huge role in physiology of gametes. The area of sperm ion channel physiology was relatively terra incognita in comparison to neuroscience and muscle physiology, and I was very excited to go there and explore. Dr. Stanley Meizel, well-known reproductive biologist, once called sperm cell a neuron with a tail, and this is indeed quite smart comparison. While sperm cell are not known to generate action potential, they resemble sensory neurons in their ability to react to various physiological cues provided by female reproductive tract and use these cues to successfully navigate in their search for the egg.

So, in late 2007, while being a postdoctoral fellow at UCSF, I decided to begin my unforgettable and fun journey into reproductive biology. This path was not without a certain risks. While reproductive biology is very important and exciting field of research, paradoxically, it is one of the least funded one. For example, NICHD funding rate is way below 10%, and very few extramural funding opportunities currently exist for students and postdoctoral researchers who decide to devote their research to reproductive biology. Myself, I have been struggling for several years to secure NIH funding, and while my lab is currently fortunate for being supported by two NIH grants: NIGMS (R01) and NICHD (R21), as well as by private funding from Pew Charitable Trust (thanks to the neuroscience portion of my research) and Alfred P. Sloan Foundation, we need to secure more research support, as the work we do requires significant investments.

various mammalian sperm

Fig. 1. Examples of sperm morphological diversity. Spermatozoa of different species are shown with cytoplasmic droplets indicated by yellow arrows. Shown are: human (Hs; Homo sapiens), mouse (Mm; Mus musculus), rat (Rn; Rattus norvegicus), rhesus macaque (Mmu; Macaca mulatta), boar (Sd; sus scrofadomesticus), and bull (Bt; Bos taurus) sperm cells.

Why should we study reproductive biology and what is there for me, may you ask? Reproductive biology field holds many surprises for everyone, and has unlimited translational potential. For example, while working on identification of non-genomic progesterone receptor of human sperm, we have uncovered a novel signaling pathway that links steroid hormones with endogenous cannabinoids. And this bioactive lipid signaling is not sperm specific, but likely plays role in various tissues. Why is this important? Steroid hormones, such as progesterone, estrogen, testosterone or other steroids control fundamental organism function by regulating gene expression via their cognate nuclear receptors. However, fast and potent non-nuclear membrane signaling can also be initiated by steroids. Such phenomena as sperm activation, egg maturation and progesterone–induced analgesia are operated via a non-nuclear pathway, the key molecular regulators of which remained unknown. After five years of search for sperm membrane progesterone receptor we have finally revealed its molecular identity- monoacylglycerol lipase ABHD2. This protein is highly expressed in sperm, possesses progesterone-stimulated hydrolase activity and directly regulate sperm principal calcium channel that is crucial for male fertility. But what we actually found, is an unconventional pathway that links steroid hormones with the levels of bioactive lipids, such as endocannabinoid monoacylglycerol and arachidonic acid. ABHD2 is a member of large ABHD family of lipid enzymes, and it is possible that other members of the same family could be influenced by other steroids in similar manner. Of course, this hypothesis requires rigorous testing and we hope that it will be done in the near future. ABHD2 is not sperm specific: it is highly expressed in testis, microglia and lungs, and all these tissues are known to be regulated by endocannabinoid monoacylglycerol- the bioactive lipid that is eliminated by ABHD2 in progesterone-dependent manner.  Therefore, targeting ABHD2 in neurons or lungs may provide a new target for novel pharmacological approaches to improve pain management, as well as treat respiratory diseases. ABHD2 can also serve as a biomarker for male fertility and may help clinicians understand why some couples are unable to conceive naturally.

The link between steroids and endocannabinoids is just one of the many surprises that gametes hold in their treasure box. These cells are more sophisticated than what we think of them and will reward greatly those researchers who dare to wonder in the unexplored fields of reproductive biology.

–Polina Lishko

 

 

Disulfide Bridge: More Than Just a Simple Bond

BPJ_110_8.c1.inddDisulfide bridges, a common type of covalent bond in protein structures, are usually believed to maintain structural stability of proteins, especially small peptides that lack hydrophobic cores.  Our study, in this April 26 issue of Biophysical Journal, revealed that disulfide bridges are also critical, at least in the case of the MCoTI-II peptide, for holding together a native structure that is frustrated.

The cover image shows the native structure (left) as well as snapshots from folding/unfolding molecular dynamics simulations of the cyclic peptide named MCoTI-II, which acts as a trypsin inhibitor in plants and has three disulfide bonds in its native state (red, green, and blue). In the context of its folding funnel, our simulations showed that the peptide is frustrated near the bottom of the funnel (native structure, middle), but not as frustrated higher up in the funnel (unfolded states, right). The formation of two of the three disulfide bridges was found to be anti-correlated when the peptide approaches the native state, yet both are critical for snapping the frustrated native structure into place. The protein structures in the cover image are visualized through VMD (http://www.ks.uiuc.edu/Research/vmd/).

When the sequence of protein isn’t perfect for folding, perhaps as a result of evolution for function, disulfide bridges can play a role holding together a frustrated structure that cannot form otherwise. Furthermore, due to the extreme stability and interesting biological activities of cyclotides such as MCoTI-II, our studies may also shed light on engineering cyclotides as novel pharmaceuticals in the future.

-Yi Zhang, Paramjit S. Bansal, David Wilson, Klaus Schulten, Martin Gruebele, Norelle L. Daly

Why Didn’t Bobbi Win a BPS Award?

You pick up the newsletter announcing the society awards, or as the awardees are recognized at the annual meeting, you think, why hasn’t “Josephine” or “Heinrich” been recognized with that award?  They should be up there…or that should be there picture on the front cover of the newsletter.  Chances are excellent that your candidate of choice may very well be eligible for the award, but nobody nominated them.

The Society Awards and Fellows program recognizes outstanding scientists for their contributions to the field in several categories. Working in science, you know these awards are a wonderful thing to have on a CV and can be of assistance in helping an individual advance in their careers. Or a chance to provide recognition for work done in education, outreach, or on behalf of the Society, that is not always given much attention in regular academic channels.  But the awards and fellows program is only as strong as the membership’s involvement in the process.

This is where you come in.  Don’t assume that someone else will nominate the person you have in mind. Take the initiative to submit the nomination yourself.  The awards, eligibility requirements, and nomination information are available on the BPS website.

You still have a week (deadline May 1)  to make a case for an amazing biophysicist to be on the stage at the BPS 2017 Annual Meeting, earning wide recognition for their contributions.

Parquets of Cardiac Tissues and the Developed Force

BPJ_110_7.inddMost of us know someone who lost their life to heart disease. Indeed, as medical science gets more sophisticated, heart disease remains the primary cause of death in the developed world. The heart is a beautifully efficient pump, with intricately arranged sheets of myofibrils producing enough force at every heart beat to propel the blood throughout the body. So what is heart disease?

When the heart’s structure, dynamics, and/or function are disrupted, the blood can no longer be efficiently pumped, which leads to a host of health complications. Finding cures is hampered by the many biophysical mysteries underpinning the efficient operation of the heart. For example, many forms of heart disease are associated with changes in cardiac myofibril organization, but how that impacts the heart’s ability to pump is unclear.

The cover image on the April 12 issue of Biophysical Journal shows a disorganized cardiac tissue that helps us understand the physical relationship between structure and function in the heart. The image is a large, 10x, view of a cardiomyocyte monolayer organized similar to a parquet floor with an arrangement of square tiles of longitudinally grained wood. To generate the sample for imaging, cardiac cells were seeded onto a parquet pattern like the one illustrated in our manuscript. The cardiomyocytes then spread out, guided by the pattern, to take on the architecture seen in the cover image. While the resultant cardiac tissue is globally disorganized, in our article, we show that such tissues produce a much higher force than disorganized tissues made from cells cultured on a uniform extracellular matrix. Using such parquet tissues, we were able to elucidate the relationship between global organization and net developed force of cardiac tissues. The discovery and experimental technique will continue to be used to understand and better design engineered cardiac tissues, including ones made from stem-cell derived cardiomyocytes.

– Meghan B. Knight, Nancy K. Drew, Linda A. McCarthy, Anna Grosberg

First Golden Goose Award of 2016 Goes to NIH-funded Social Science Researchers

Ce0-qDSWQAIRhtTRESEARCHERS BEHIND LANDMARK ADOLESCENT HEALTH STUDY – A STUDY
THAT ALMOST DIDN’T HAPPEN – WILL RECEIVE GOLDEN GOOSE AWARD,

Five researchers whose determined pursuit of knowledge about the factors that influence
adolescent health led to one of the most influential longitudinal studies of human health—with far-reaching and often unanticipated impacts on society—will receive the first 2016 Golden Goose Award.

The researchers are Dr. Peter Bearman, Barbara Entwisle, Kathleen Mullan Harris, Ronald
Rindfuss, and Richard Udry, who worked at the University of North Carolina at Chapel Hill
(UNC) in the late 1980s and early 1990s to design and execute the National Longitudinal Study of Adolescent Health, or Add Health for short.

The social scientists’ landmark, federally funded study has not only illuminated the impact of social and environmental factors on adolescent health—often in unanticipated ways—but also continues to help shape the national conversation around human health. Their work has provided unanticipated insights into how adolescent health affects well being long into adulthood and has laid essential groundwork for research into the nation’s obesity epidemic over the past two decades.

“Four bold researchers wanted to learn more about adolescent health. Who knew that one federal study would change the way doctors approach everything from AIDS to obesity?” said Rep. Jim Cooper (D-TN), who first proposed the Golden Goose Award. “Decades later, this work is still paying off, helping Americans lead longer, healthier lives. America always comes out ahead when we invest in scientific research.”

The pathbreaking nationally representative Add Health study has answered many questions about adolescent behavior, with particular attention to sexual and other risky behaviors, but it was almost stopped in its tracks by political concerns.The study’s design grew out of the American Teenage Study, a project developed by Drs.Bearman, Entwisle, Rindfuss, and Udry. This initial adolescent sexual health study was designed to look at adolescents’ risky behaviors in a social context, rather than focusing only on individuals, in hopes of helping the nation address the growing AIDS epidemic and other public
health concerns. After two years of planning work funded by the National Institutes of Health (NIH), the American Teenage Study passed peer review and was funded by the NIH in 1991. But the grant was subsequently rescinded due to objections regarding the study’s focus on sexual behaviors.

In 1993, Congress passed legislation forbidding the NIH from funding the American Teenage Study in the future, but at the same time mandating a longitudinal study on adolescent health that would consider all behaviors related to their health – implicitly including sexual behavior.

“I congratulate Dr. Rindfuss and his colleagues on this award, which underscores the vital
importance of federal funding for research,” said Rep. David Price (D-NC), who was a key
advocate in the House of Representatives in the 1990’s for continuing to pursue this research. “Federally supported research projects not only produce new life-saving treatments and expand our understanding of the world around us, they also spur economic growth and innovation in ways we cannot always anticipate.”

In 1994, Drs. Udry and Bearman, now joined at UNC by Dr. Harris, proposed Add Health to
meet Congress’s new mandate. The new study maintained the American Teenage Study design’s strong focus on social context, but significantly expanded the scope of inquiry to include all factors influencing adolescent health. The study has followed its original cohort for over 20 years, and it is now providing valuable information about the unanticipated impacts of adolescent health on overall well-being in adulthood. For this reason, the researchers recently changed the study’s name to the National Longitudinal Study of Adolescent to Adult Health, and it is a landmark example of how longitudinal research can yield extraordinary and unexpected insights.

“Science often advances our understanding of the world in ways we could never have foreseen,” Rep. Bob Dold (R-IL) said. “Regardless of how this research began, it has served as a breakthrough for understanding the way society molds our personal health. That’s why congressional funding and support for breakthrough research is so important to push us forward as a country.”

The nationally representative sample and multifaceted longitudinal data paired with a
revolutionary open-access model have enabled more than 10,000 researchers to publish almost 3,000 research articles on human health. These scientific studies have strengthened an understanding of the importance of family connectedness to adolescent health, allowed researchers to track and scrutinize the rising tide of the obesity epidemic, and demonstrated the social, behavioral, and biological importance of adolescence to lifelong health and wellbeing.

What began as a study driven both by social science curiosity and public-health concerns has been central to shaping the national conversation around adolescent health for more than two decades.

The Golden Goose Award honors scientists whose federally funded work may have seemed odd or obscure when it was first conducted but has resulted in significant benefits to society. Drs. Bearman, Entwisle, Harris, Rindfuss and Udry are being cited for their extraordinary multidisciplinary, longitudinal study of the social and biological factors that influence adolescent health, and their work’s wide-ranging and often unexpected impacts on society. The five researchers will be honored with two other teams of researchers – yet to be named – at the fifth annual Golden Goose Award Ceremony at the Library of Congress on September 22.

About the Golden Goose Award
The Golden Goose Award is the brainchild of Rep. Jim Cooper, who first had the idea for the award when the late Senator William Proxmire (D-WI) was issuing the Golden Fleece Award to target wasteful federal spending and often targeted peer-reviewed science because it sounded odd. Rep. Cooper believed such an award was needed to counter the false impression that odd sounding research was not useful. In 2012, a coalition of business, university, and scientific organizations created the Golden Goose Award. Like the bipartisan group of Members of Congress who support the Golden Goose Award, the founding organizations believe that federally funded basic scientific research is the cornerstone of American innovation and essential to our economic growth, health, global competitiveness, and national security. Award recipients are selected by a panel of respected scientists and university research leaders.

The Biophysical Society has been a sponsor of the award for the past three years.

The Science Behind the Image Contest Winners: Light Trails of Receptor Tyrosine Kinase EphA2

The BPS Art of Science Image Contest took place again this year, during the 60th Annual Meeting in Los Angeles. The image that won second place was submitted by Thomas Newport, a PhD student at the University of Oxford. His image shows simulated dynamics of the ectodomain of the receptor tyrosine kinase EphA2 (shown as glowing lines) as well as different conformations that highlight the possible movement of this receptor relative to the membrane surface. Newport writes here about the image and the science it represents, as well as his experience as a first-time BPS Annual Meeting attendee.

Newport Thomas-57-84474

The Biophysical Society’s 2016 meeting was unlike any other conference I have attended in my admittedly fairly short academic career. Thousands of posters, talks, and exhibits clamour for attention over a packed six day schedule. Distinguished professors haggle over conclusions with terrified grad students, while suited salespeople draw in new customers with the promise of free bags, USB drives, and flat-pack microscopes.

Probably the highlight of this, my first Biophysical Society meeting, was winning second prize in the Art of Science image competition, or as my supervisor helpfully emailed me a few minutes later, “congratulations, you’ve won second prize in a beauty contest, collect $10.” The competition: ten gorgeous images, some computer generated, some from microscopes, telling a selection of stories from across the vast field of biophysics.

My image was developed in collaboration with Matthieu Chavent, and shows simulated motions of a key signalling protein as it interacts with the cell membrane. His paper explains more of the scientific background and is well worth a read. Matthieu had already visualised the protein using VMD, a popular open source visualisation tool for molecular dynamics simulations, and traced the paths followed by several atoms as the protein moved between two states. By this point my enthusiasm for digital art and 3D visualisation was fairly well known so we met up to discuss turning this data into art.

Blender3D has been my tool of choice for 3D digital art since I was in high school. It’s open source, has great developer and user communities, and can be used for anything from game development to movie production. Working on the data in Blender gave me complete control of the scene, letting me get the composition, lighting and materials just right. I drew inspiration from long-exposure “light painting” photography, where movement can be captured using trails of light. The light trails were probably the most difficult part to get right – transparent and glowing enough to look ethereal but clear enough to be easy to follow.

It seems to have been a hit – the image has been used as the cover of Structure journal and even appeared on the 2015 Biochemistry Department Christmas card (Matthieu even photoshopped some festive hats onto the proteins, although sadly they didn’t make it to the final card). I’ve run a couple of courses teaching Blender to structural biologists, and it definitely seems like a few people were put off by easily fixable data compatibility issues. Once I’ve got a moment free I’d really like to improve the way Blender handles structural biology data to take some of the data wrangling out of developing scientific art. If you’d like to help, you can find me on GitHub or Twitter (@tnewport).

Concepts in biophysics and structural biology are often most effectively communicated through images, from the iconic double helix of DNA to Jane Richardson’s now ubiquitous protein ribbon diagrams. New technologies are creating new ways for us to tell scientific stories in visual media, as still images, videos, and interactivities. This year’s BPS Art of Science competition showcased some amazing works of art that have come out of these advances, and I’m looking forward to an even tougher competition next year.