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FRETing about Protein Dynamics: Keith Weninger

09/23/2013

Our Virtual Symposium profile series continues with Keith Weninger from North Carolina State University. Weninger earned his doctorate at the University of California, Los Angeles before moving to Stanford University for a postdoctoral fellowship. In 2004, he accepted a faculty position in the Department of Physics at NCSU. His current research centers on exploring protein dynamics in DNA mismatch repair and membrane fusion using single molecule biophysics approaches including single molecule FRET.


How did you get started in science?

I guess I have always been surrounded by science–even as a kid my parents discussed scientific things with me. Then, as an undergraduate, I had a number of great teachers and mentors who continuously inspired me to dive deeper and deeper in my understanding of different fields of science. I never really stopped after that.

What is your main research focus?

Currently, I’m very interested in the dynamic structural changes in proteins that enable their different functions. Single molecule FRET is my main tool here because it is uniquely sensitive to molecular conformational dynamics, and it can be used in many assays where proteins perform their natural functions.

The scientific questions I pursue are focused on two distinct phenomena: proteins responsible for catalyzing the membrane fusion reaction resulting in neurotransmitter release at synapses and the protein system that identifies DNA mismatches and signals for their repair.

How did you get into your current field of research?

I came into biophysics research later in my education. Most of my formal training was in physics and did not involve biology. Therefore, I have been very careful to work with collaborators for my biophysics efforts. My interest in neurotransmitter release proteins started during my first postdoctoral fellowship in biophysics. Actually, this was the first collaboration opportunity that was presented to me, and I have never let go of it.

Our DNA mismatch repair studies actually started when Lauryn Sass, a graduate student at another university, found me through a Google search. She was in a lab using atomic force microscopy (AFM) and she, and her advisor, approached me with any idea to use FRET with her experiments. So, we started a collaboration that has taken off to the point where now, 8 years later, it is the main focus of my group.

For you, what is the most exciting open question in your field at the moment?

While DNA mismatch repair reactions have been reconstituted in vitro for more than a decade, important questions remain about how the participants in this process communicate. DNA mismatch repair is active at double-strand DNA base pairs where one DNA base is correct and the opposing base is incorrect, forming a non-canonical pair. The most exciting questions revolve around the mechanisms by which proteins decide which side of the mismatched pair to excise and resynthesize as the correct complement. If the system picks wrong, then rather than repairing the mismatch, the error is propagated. How this information is obtained and then passed through the cascade of DNA repair proteins remains a key unknown in the field. And this is incredibly important because failures in this system of proteins are associated with diseases, the foremost of which is cancer.

As we are a methods journal, what do you see as the most pressing "method" need in your field?

My experiments are all based around fluorescence interrogation of proteins. Cysteine engineering is the most commonly used approach, but it can’t be used with many proteins. So, one of the biggest methodological limitations holding us back at the moment is the lack of a simple, but robust, method for site-specific labeling with fluorescence probes that is more generally applicable than cysteine manipulation. There are several emerging approaches that use enzymatic processes lifted from natural biological pathways, but these are still early in development and have not spread far beyond the labs where they originated.

What suggestions/recommendations do you have for scientists starting on their careers now?

I always advise people to follow their interests and enjoy what they are doing. Careers in science have many difficulties and challenges, so if you don’t enjoy what you are doing, you will not have the motivation to excel.

My other piece of advice is to be flexible in your interests and pursue many different types of training and knowledge. The more diverse your skill set, the more complex the problem you can attack.

You are a speaker at the 2013 BioTechniques Virtual Sympoisum. What are you looking forward to about presenting at this year’s Virtual Symposium?

I look forward to the opportunity to present my work to a more diverse audience than I usually get to speak to. This virtual symposium will allow me to make new connections with people working in fields that I don’t usually get to interact with.

What do you think about the concept of “virtual” education in general? Is this your first ‘virtual presentation’? Have you been involved with other online education efforts such as MOOCs?

Virtual education will grow in the future as the technologies for electronic based communication evolve and the efficiencies of this mode of delivery are appreciated. With one of my colleagues, Professor Laura Clarke, I have taught an online course at North Carolina State for a few years now. However, our course is in some ways the complete opposite of a MOOC; this course is intentionally kept very small, aimed at in-service high school physics teachers.

Many high school physics teachers were originally trained in chemistry or biology, but are asked to teach physics because specialized high school physics teachers are in short supply. My course seeks to improve their understanding of the content of college level physics curricula. The distance education format of the course is essential because it allows the teachers to maintain their current full-time position in the high school classroom while taking a challenging college course. I use many of the state of the art technologies developed for virtual presentations and distance-based conversations to engage the teachers, but the difference with a MOOC is that in my small course the participants are provided with extensive interaction and feedback. Our virtual course must be kept small to enable such personalized interaction. The real challenge for MOOCs is to develop a scalable way for an authority to provide feedback to students and to moderate discussions among participants.

Learn more about Keith Weninger's upcoming talk at the Biotechniques Virtual Symposium website.

Keywords:  Profile