Using Biophysics to Understand Diabetes

November is National Diabetes Month in the United States. Twenty-nine million people in the US live with diabetes. To recognize this awareness month, we spoke with BPS member Roger Cooke, University of California, San Francisco, about his biophysics research related to the disease.

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This cartoon shows the 3 states of myosin. In the active state the myosin head is attached to the actin filament producing force and motility. In the super relaxed state, shown above, myosin heads are bound to the core of the thick filament, where they have a very low ATPase activity. In the disordered relaxed state myosin heads extend away from the core of the thick filament where they have a much higher ATPase activity and are available for binding to actin.

What is the connection between your research and diabetes?

Our laboratory has studied the physiology and biophysics of skeletal muscle for many decades. Recently we have concentrated on the metabolic rate of resting skeletal muscle. Skeletal muscle plays a major role in diabetes as it is the organ response for metabolizing a large fraction of the carbohydrate that we consume. Recently we have discovered a mechanism, which we believe can be manipulated to up regulate the metabolic rate of resting muscle, thus metabolizing more carbohydrate. This would be particularly helpful in Type 2 diabetes.

Why is your research important to those concerned about diabetes?

Type 2 diabetes is thought to be caused by or an overconsumption of carbohydrate coupled with a sedentary lifestyle that does not need the carbohydrate as fuel.  The excess carbohydrate leads to high levels of serum glucose. Our laboratory has focused on the motor protein myosin, which is responsible for producing the force of active muscle and also responsible for using much of the energy ingested in the form of lipids and carbohydrates. We have shown that myosin in resting muscle has 2 states with vastly different functions and metabolic rates. In one of these, the super relaxed state, the myosin is bound to the core of the thick filament where its metabolic rate is inhibited, See Figure.  In the other, the disordered relaxed state, the myosin is free to move about and its metabolic rate is more than10 fold higher.  By analogy with another motor, myosin in active muscles is akin to a car racing down the road. Myosin in the disordered relaxed state is similar to a car stopped at a traffic light with the motor idling, and the counterpart of the super relaxed state is a car parked beside the road with the motor off.

For energy economy in resting muscle most of our myosins are in the super relaxed state. If all of these myosins were transferred out of the super relaxed state into the disordered relaxed state they would consume an additional 1000 kilo calories a day. This is a large fraction of the standard daily consumption, which is approximately 2000 kilo calories a day.  Thus a pharmaceutical that destabilized the super relaxed state would lead to the metabolism of a greater amount of carbohydrate providing an effective therapy for Type 2 diabetes. Such a pharmaceutical would address one of the fundamental problems in Type 2 diabetes the consumption of more carbohydrates than are required as fuel.

How did you get into this area of research?

In 1978 a group in England showed that purified myosin in a test tube had a much greater activity than it has in living fibers. This observation showed that myosin in vivo spent much of its time in a state that had a very low metabolic rate. I felt that this inhibited state of myosin could have important consequences for resting muscle and whole body metabolic rates. Although we studied this problem for a number of years, we were not able to find an in vitro system that replicates the in vivo activity. In 2009 we started using quantitative epi-fluorescence spectroscopy to measure single nucleotide turnovers in relaxed skinned muscle fibers, and finally we were able to observe the elusive inhibited state of myosin, the super relaxed state.  This ability allowed us to now study the properties of this state.

How long have you been working on it?

I have been interested in this problem since the original observation in 1978, described above. However it was not until 2009, and the discovery of the in vitro assays, which allowed us to observe the super relaxed state, that this project became the central focus of our laboratory.

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

Our work has been funded by the National Institutes of Health.

Have you had any surprise findings thus far?

The Holy Grail in this area of research is to find pharmaceuticals that will destabilize the super relaxed state. Recently we were able to devise new methods of measuring the population of the super relaxed state, methods that were amenable to use in high throughput screens. We screened over 2000 compounds looking for ones that destabilized the super relaxed state.   We found only one compound that did so, a compound named piperine, which provides the pungent taste in black pepper. After working for over a year developing assays and running the screen, to our surprise the one molecule we discovered was already known to mitigate Type 2 diabetes in rodents. Although piperine lowered serum glucose, no one knew how it did this. We propose that piperine acts by destabilizing the super relaxed state, thus up-regulating the metabolic rate of resting skeletal muscles. We showed that piperine had no effect on active muscle and no affect in cardiac muscle, both desirable qualities to have in a pharmaceutical targeting resting skeletal muscle to treat Type 2 diabetes. Although piperine is effective in lowering blood glucose in rodents, it only does so at very high doses, too high to be useful as a therapeutic in humans.  We now need to find molecules whose action is similar to piperine, but which bind with greater affinity.

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

Our results provide the proof of concept that pharmaceuticals targeting resting muscle metabolic rate, can be found, using the high throughput screens we developed.  These new pharmaceuticals have the potential of more effectively treating Type 2 diabetes.

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

Type 2 diabetes is a growing problem worldwide. Almost 10% of the US public has Type 2 diabetes.  Our research holds out the hope that new pharmaceuticals will be found to treat this disorder more effectively than those available today.

Our studies have also shown that the super relaxed state is destabilized when muscles are activated, and that it will remain destabilized for a number of minutes afterwards, due to phosphorylation of myosin. This extended period of destabilization adds to the metabolic cost of activity, particularly during light and intermittent activities. In fact a number of studies have shown that even modest and intermittent activity will improve serum glucose, help prevent weight gain and lead to better health. The worst thing that people can do is to sit for extended periods of in front of a computer or TV screen. For example when working at a computer I get up and walk around the room every 10 minutes or so, and I avoid elevators, taking the stairs to my laboratory on the 4th floor.

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Everything You Need to Know about BPS Travel Awards for the 2017 Annual Meeting

A month remains before the abstract and travel award deadlines for the Biophysical Society’s 61st Annual Meeting, being held in New Orleans, Louisiana, February 11-15, 2017. If you are a student, postdoc, early or mid-career scientist looking for a little extra funding to attend the Annual Meeting, be sure to apply for a BPS Travel Award. Check out the FAQ below to learn more about the application process.

What is the Travel Award application deadline?

October 5. Remember: You MUST submit an abstract by October 3 in order to be eligible for a Travel Award.

Can I submit any part of my application late?

No. ALL parts of your application are due by the October 5 deadline – including your letters of recommendation! Start asking your advisers for references now, and be sure to read each award’s description so you know exactly what is required.

I think I’m qualified for more than one award. Can I apply for multiple awards?

Yes, you can apply for multiple travel awards, as many as you are eligible for. However, you can only be selected to WIN one award.

 Oops! I forgot to submit my abstract by October 3. But I am going to submit a late abstract! Can I still apply for a Travel Award?

No. Only abstracts submitted by the regular abstract deadline (October 3) will be eligible for a Travel Award.

I am a co-author on an abstract, but not a presenting author. Can I apply for a Travel Award?

In most cases, no. For all Education, CID, and International awards, you MUST be a presenting author on the abstract. If you are not a presenting author, your abstract will be marked as ineligible. This also applies to CPOW awards for postdocs. For the mid-career CPOW award and the Bridging Funds, you must be a co-author or presenting author on a submitted abstract.

When will I find out if I won?
You will be notified on the outcome of your application via email by November 23. Be sure to check your spam folder if you don’t see the email.

My adviser would rather send the letter of recommendation directly to you. Where exactly should he/she send it?

Letters of recommendation can be emailed to lphelan@biophysics.org. All letters must be received by the October 5 deadline.

 I am not a US citizen, but I am still a minority researching in the US. Why can’t I apply for the CID Travel Award?

Because the CID Travel Awards are funded by an NIH grant, only US citizens or permanent US residents are eligible. Be sure to check out the Education or CPOW awards to see if you qualify.

I am currently a graduate student. However, by the time of the Annual Meeting I will be a postdoc. What award should I apply for?

You should apply for the awards that fits your career level as of October 5. In this case, you must apply as a graduate student.

I am no longer a student or a postdoc. Am I eligible for a Travel Award?

CID, CPOW, International Relations Committee travel awards and Bridging Funds are available for junior, senior, and/or mid-career scientists. Please check eligibility requirements online to see if you qualify for any of these awards.

 

Have additional questions? Please contact the Society Office at (240)-290-5600 or lphelan@biophysics.org.

 

Biophysical Society Summer Research Program: The Time of Your Life

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

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

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

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

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

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

BPS Summer Research Program Alumni Reunion: A Current Student’s Perspective

From June 17-19 the Biophysical Society’s Summer Program in Biophysics hosted its annual Alumni Reunion Weekend in Chapel Hill, North Carolina. Previous program participants joined the current class for a fun and informative weekend that included a BBQ reception, scientific presentations from program alumni, career talks and panels featuring a diverse group of visiting scientists, as well as poster presentations by students from the current class. Students, alumni, and professors had a chance to catch up, network, and even make a few new friends over the course of the weekend. Current students received feedback on their posters and guidance on navigating their careers, along with the opportunity to ask questions on a variety of topics. In this blog, we will hear from current BPS Summer Program participant, Monica Cortez, on her thoughts about the reunion weekend.

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The Biophysical Society’s 2016 Summer Program Alumni Reunion Weekend was my first experience participating in an event where I had the opportunity to present my research. The weekend’s poster session went well and I was able to discuss my research with alumni, current students, program staff, and visiting scientists. During the session, one scientist approached me with a mini experiment she was conducting on students during the poster session: I was dealt the task of explaining my project to her as if she were a time traveler from the 1800s. At first I was nervous about the approach to explaining my project in an elementary way, but much to my surprise, I quickly uncovered my talent for science communication. As a scientist, it is important to be able to communicate your research to anyone ranging from the general public to the most knowledgeable scientists. There was a lot of fun to be had explaining my project in breaking it down to the bare bones of it, the most fundamental concepts going into the big picture of the research. I realized then that my ability to simplify the explanation of my project meant my mentor had done an excellent job in helping me understand my project.

As the poster session proceeded, groups would rotate, and some people would linger a little longer if something caught their interest or if they needed further clarification about the project. This brought me to my next challenge, the challenge of defending previous work done on the project; work done by other researchers collaborating on the project. This means that I was asked questions about the research that I had not asked myself previously. One particular question involved a technique I had not done previously. My first time doing the technique was less than 24 hours before the question was asked. This was a frustrating moment during the poster session. The conversation about a tiny but very important detail to the project felt like it went on for hours. As my first poster session and first experience presenting my “explanation of research” experience, I felt targeted by the question, but I walked away from it with a new understanding. This understanding is that you will be asked questions you did not think about, and you will have to answer truthfully that you do not know the answer to their question. It is not a matter of being targeted, rather it is a matter of realizing research is about answering questions no one knows the answer to.

On the concluding day of the weekend, Summer Program alumni presented their own research and took part in a career panel. This day, program alum, Dr. Yadilette Rivera-Colón provided feedback about the “time traveler” experiment she conducted and went on to explain her background and her path to get where she is today. Congratulations to her because she announced her next career move: an associate professor position! It was amazing to sit amongst a crowd seeing one of our very own alumni finally serving in academia as a professor. Another alum spoke on getting NSF grants and provided tips on how to apply. There were also alumni who spoke on taking steps towards other career opportunities outside of academia. I felt that this was a good choice of topic and beneficial to expose the current Biophysical Society’s Summer Program students to alternative career choices. The career panel was also beneficial in that it led to interesting discussions. One particular point I feel is important to mention is the commonality among the scientists on the panel: even though their paths were very different, they all overcame potential roadblocks encountered by building an excellent support system. One very emotional topic involved the journey to getting a PhD; many panelists felt a lack of excitement and emotional support from their advisors when passing their candidacy, being given a small “congratulations” and a “so what’s next for experiments?”. I was taken aback by this because I’ve always surrounded myself in a good network of people who get excited over my accomplishments no matter how big or small they are. This emotional experience was important for the summer students to witness, highlighting how a strong support system and communication skills play a huge part in success. Communication of your work as a scientist is important, but more importantly the communication between you and your advisor/boss is even more important. Once the emotional needs of the mentee are efficiently communicated to the mentor, their relationship can strengthen. Your mentor/mentee relationship is an important part to succeeding in graduate school and beyond. Several alumni candidly discussed how not meeting these emotional needs can lead to crippling depression during graduate school, and encouraged current students to utilize the Program’s alumni network as a source of ongoing support throughout their careers.

The weekend concluded differently than I had expected but overall I wouldn’t have changed anything about this experience. The summer students met people from different career paths and learned how to communicate. Being a part of this summer program feels like a privilege. Not only was I blessed with an advisor who helped me accomplish this part of my career journey, but I am blessed to be working on a project with an excellent mentor here at UNC who is extremely supportive as well. This weekend showed me that I also have a network of alumni from the Biophysical Society’s Summer Research program; an important connection between previous students and the current students has been established, and we are so lucky to have met them all.

 – Monica K Cortez, Biophysical Society Summer Research Program Fellow

BPS Summer Program Alumni Spotlight: Yadilette Rivera-Colón

The Society recently caught up with 2008 Biophysical Society Summer Program in Biophysics alumna and active member of the BPS Education Committee, Yadilette Rivera-Colón. Since participating in the program as an undergraduate, Yadilette has gone on to receive her PhD in Molecular and Cellular Biology from the University of Massachusetts, Amherst and complete a post-doctoral fellowship at the University of Pennsylvania. Read more about her life and career in her 2014 profile in the BPS newsletter. This August, Yadilette will begin a new, exciting chapter in her career.

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Tell us about where you are now in your career.

I just attained my first faculty position at Bay Path University. Starting this fall, I will begin my roles as an undergraduate research coordinator and assistant professor in biology.

What excites you most about starting this new position?

The most exciting aspect of this new position is the fact that I will get to educate not just within the school but also the community as a whole.  There are many underserved students in that area and I want to be able to create educational opportunities for them so that they know how many options are available for them. I am looking forward to try innovative teaching methods and one of the reasons I joined Bay Path University is because it is an environment where professors are encouraged to do so.

What is your research focus?

I plan to study novel acetyltransferases and gain insight into their structure and function using exciting directed evolution approaches.

When and how did you first become interested in this type of research?

I first developed an interest in protein structural biology as an undergraduate summer student while studying T7 Polymerase in Dr. Craig T. Martin’s lab at UMass Amherst.

How have mentors played a role in shaping your success?

Yes! In addition to working closely with your thesis advisor, it is important to surround yourself with mentors that have supplementary skills, strengths, and areas of expertise. Dr. Craig T. Martin, Dr. Jeanne Hardy, Dr. Sandra Petersen, Dr. Barbara Osborne, Dr. Scott C. Garman (my thesis advisor), and Dr. Ronen Marmorstein (my post-doc advisor) were all critical to my success as a scientist. My amazing teaching mentors, Dr. Sandra Devenny and Dr. Georgia Arbuckle, were similarly important to my development as a teacher. These professors helped me with everything from improving my grammar to developing confidence to designing efficient and informative experiments. I have also found mentors in my undergraduate students: Emily Schutsky, Sarah Tarullo, Shaul Kushinsky, Andrew Maguire, and Nada Bader. They always kept me grounded and helped me remember what it is like at the beginning of your scientific career.

What have been some of your toughest challenges so far in advancing your career?

So many challenges! In addition to the new language, moving to the main land from Puerto Rico presented a variety of weather and cultural differences. From the necessity of buying a winter coat, to shaking hands firmly rather than hugging and kissing to say “hi,” I found grad school life to be a bit colder than what I was used to. I felt a certain amount of pressure to conform to the quieter, less colorful personal and professional styles shown by my some of my classmates. Over time, however, I have learned a lot about other cultures and how amazing it is to have perspectives of people from very different backgrounds. There were times when I struggled with the fact that some people achieve their goals more quickly than others, but I have learned that there is nothing wrong with being a bit slower, as you can still accomplish the goals you have set for yourself.

What was the most important thing you learned or took away from the Biophysical Society’s Summer Program that helped you get where you are at now?

Dr. Martin told me about the Summer Course in Biophysics, and it has been one of the most instrumental aspects of my development as a scientist. My current success would be unimaginable without the amazing support network of professors and colleagues that I cultivated there.

What was your favorite thing about participating in the summer program?

I really enjoyed the opportunity to study with students from different academic and ethnic backgrounds, especially when working together on our homework. Everyone I collaborated with had a different area of expertise, and we helped each other learn challenging new concepts in a really fun, diverse environment.

What advice would you give for current undergraduates interested in pursuing a higher degree?

Keep your career options open and learn about everything. You never know what skills or connections will help you in the future, so keep learning and keep growing your professional network!

BPS Summer Program Alumni Spotlight: Joshua Mannheimer

Josh_Mannheimer_PhotoWe recently had a chance to interview Joshua Mannheimer, an alumnus of the 2013 Biophysical Society Summer Program in Biophysics, and learn about what he has been up to since his time in the Summer Program. Currently, Joshua is at Colorado State University wrapping up his Master of Engineering Degree in mechanical engineering after which he will be directly matriculating into the Biomedical Engineering PhD program.

What is your research focus?

I consider myself an applied computational biophysicist. My goal is to use computational tools to guide experimental scientists by providing insight into biological processes through modeling. Additionally, I am interested in developing computational tools to assist in clinical medicine. My current project uses advanced statistical techniques, called machine learning, to predict the efficacy of chemotherapeutic agents on certain cancer types based on genetic analysis.

When and how did you first become interested in this type of research?

I really got interested in biology in high school, but after taking physics my senior year I decided to get my BS in physics. After a couple years of pursuing physics I had decided to take a few chemical and biological engineering courses; it was through these courses I was connected with a faculty member in the Biomedical Engineering department who happened to have a background in physics. It was through him that I realized the potential to use physics-based models to probe questions in biology.

In terms of what I do right now, it was actually quite serendipitous. After my first year in the ME program I was looking for an internship in industry to build experience professionally. After this did not work out, I needed to do something for the summer. I contacted a faculty member in the Biomedical Engineering department who happened to need someone experienced with programming. This is how I learned about big data and machine learning and was immediately aware of how big of an impact this could have on clinical medicine.

Have mentors played a role in your success?

I have been fortunate enough to have many mentors play a role in my life from school teachers who fostered my curiosity, many adults whom I looked up to as a kid who always encouraged me, and of course some of the faculty I have worked for over the years who invested time in my development as a scientist. Most importantly I have always had a supportive family.

What have been some of your toughest challenges so far in advancing your career?

I was diagnosed with Obsessive Compulsive Disorder (OCD) early in my childhood and that has by far been the biggest obstacle I have faced growing up. It impacts the way I learn and work when it comes directly to academic pursuits; however, managing my mental health while in a demanding program has been the biggest challenge, one I still struggle with but which makes me even more determined to succeed.

What was the most important thing you learned or took away from the summer program that helped you get to where you are at now?

I participated in the summer program right after I had graduated with my BS. At that point I had felt a little dismayed because I had just finished this really demanding degree and I still felt like I knew nothing. During the summer course I realized that what I really learned was how to solve problems and was impressed with how I could implement these skills to work on novel problems. It really put things into perspective.

What was your favorite thing about the summer program?

I really enjoyed the people. It was really beneficial to work with people who came from different academic backgrounds but more importantly to meet new people from different backgrounds and places.

What advice would you give for current undergraduates interested in pursuing a higher degree?

I would encourage any student to research the opportunities a graduate degree affords them and how that degree, and more importantly that research area, will lead to employment opportunities in industry and academia. After all, a degree is not useful unless you can use it.

Biophysics Research and Lyme Disease

May is Lyme Disease Awareness Month in the US. Lyme disease is a bacterial infection primarily transmitted by Ixodes ticks (known as deer ticks) and black-legged ticks that can cause a wide variety of both temporary and chronic symptoms. The CDC estimates that 300,000 people are diagnosed with Lyme disease in the US every year, but Lyme disease is easily misdiagnosed, so the actual number with the disease could be significantly higher. We recently spoke with Biophysical Society member Charles Wolgemuth, University of Arizona, about his research on the bacterium that causes Lyme disease.

What is the connection between your research and Lyme disease?

Many cells are able to actively move themselves through their surroundings.  In order to do this, the cells must exert forces on their environment.  One of the main questions that my research asks is how do cells produce these forces and how do these forces drive the movements of the cells through various environments.  The bacterium that causes Lyme disease, Borrelia burgdorferi, is a fascinating organism.  It is very long (for a bacterium) and is quite thin (being only 300 nm in diameter).  It is also one of the most invasive mammalian pathogens, being able to invade many tissues in the mammal that other bacteria cannot access.  It “swims” through different tissues by undulating its entire body.  We are currently working to understand what about this bacterium’s motility makes it so adept at invading mammalian tissue, a critical aspect of the disease process in Lyme disease.

MATLAB Handle Graphics

This cartoon schematic shows the basic structure of these bacteria. The cell body is green and the helical filaments (flagella) are shown in purple. There are 7-11 flagella per cell end and they are anchored to tiny rotary motors. If you were to peel the flagella away from the cell body, the cell would straighten (as shown on the left side of the schematic).

Why is your research important to those concerned about Lyme disease?

Lyme disease occurs when a person is bitten by an Ixodes scapularis tick, a species of hard tick, infected with Borrelia burgdorferi.  These ticks feed for approximately 4-7 days.  The bacteria reside in the midgut of the tick.  During feeding, the bacteria start replicating and eventually (after about 40 hours) some of the bacteria break through the lining of the tick midgut and swim to the salivary glands.  The bacteria then break into the salivary glands and are deposited in the skin of the mammal through the tick saliva.  Once in the skin, the bacteria are able to move through the mammalian body, infecting many tissues such as the skin, joints, heart, and nervous system.  In order to do all this, these bacteria must be able to maneuver through a large range of different environments.  The symptoms of Lyme disease are caused by our bodies trying to fight off the bacterial infection.  It has been shown that the motility of B. burgdorferi is imperative for the bacterium to set up infection.  Therefore, understanding how this bacterium is so invasive and how its movement allows it to set up infection and evade our immune system is crucial for understanding this disease.

How did you get into this area of research?

Since graduate school, I have been fascinated by figuring out how different cells create the shapes of their bodies and how they move from place to place.  I got into working on Lyme disease when I heard about the shape of B. burgdorferi.  It is shaped like a wave! and achieves this by wrapping helical filaments around a cylindrical body.  The physics for how this works out was perplexing to me and captivated my interest.

How long have you been working on it?

I have been working on this for nearly 15 years.  I started thinking about the problem while I was a postdoc at UC Berkeley and then wrote a grant to work on the shape of B. burgdorferi during my first academic appointment at the University of Connecticut Health Center.

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

We receive funding for this research from the National Institutes of Health.

Have you had any surprise findings thus far?

One of the first really exciting findings that we had was that we were able to show that the movements of these bacteria through gelatin (such as unsweetened Jello) is very similar to the movements through our skin.  Gelatin is basically a meshwork of protein, which is also true about the dermis of our skin.  Interestingly, the pores in the gelatin are substantially smaller than the diameter of these bacteria.  Therefore, B. burgdorferi has to push apart the gelatin in order to penetrate into it.  This finding has enabled us to develop an in vitro assay for studying how these bacteria invade into different tissues.  We have a couple really new results realted to invasion and the movement through gelatin that we are very excited about.  We haven’t published them yet, so I can’t say too much more than that at this time.

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

I can’t speak for other researchers, but I think that one of the most interesting aspects of our work is that we have been able to link the physics of how these bacteria move to aspects of the disease process.  We recently developed a mathematical model for the early stages of Lyme disease that is based on the physics that we have determined from our gelatin assays.   We were able to show using this model why the rash that accompanies Lyme disease sometimes appear as a bull’s eye pattern.  The model also explains why these rashes grow so fast (around 1 cm in diameter per day).  The ability to go from the basic physics of the movement of these bacteria to an understanding of the disease itself I think is especially exciting.

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

I would have to say the same thing that I just said:  We have shown that understanding the basic science of these organisms is informative about the disease process. Fifteen years ago when I started working on this, people would ask me what I was working on, and I would tell them that I was trying to figure out how the bacterium that causes Lyme disease creates its shape.  I would often get asked then about the practical application of figuring that out: how would understanding the shape of the bacterium help fight the disease?  How should I respond to this?  At that point of time, I didn’t know what we would figure out.  But it didn’t matter to me; it was an interesting question.  The way I see it, basic knowledge is worth an infinite amount more than any specific practical application.  Knowledge can be built upon and used in ways that no one can predict ahead of time.

With that, I will conclude with one thought for the general public: We must keep funding basic scientific questions, because we never know where a specific line of inquiry may lead us.  Science is not about foreseeable practical ends; it is about discovering things we never thought we would find.