By Jean Andrews
Physics & Astronomy
Doctoral student Christopher Johnson explains his research to Dr. Peter Jung at a recent Ohio University Student Research and Creative Activity Expo. Johnson presented part of this research at the Axonal Transport & Neuronal Mechanics Workshop at OSU.
“This experience opened my eyes on the seeing the importance of collaboration between different disciplines.” – Chris Johnson
Christopher Johnson, a doctoral student in the Department of Physics & Astronomy and member of the Quantitative Biology Institute at Ohio University, joined doctoral student Daniel Fenn, from the Department of Neuroscience at The Ohio State University College of Medicine, to present an invited talk “Is the Axonal Transport of Neurofilaments a Tug-of-War?” at the recent Axonal Transport & Neuronal Mechanics Workshop, a meeting sponsored by the Mathematical Biological Institute (MBI) at Ohio State University.
Workshop organizers sought to bring together leading cell biologists, engineers, physicists, and mathematicians to openly discuss exciting new findings, long-standing questions, and the future of the field.
A fundamental question in neurobiology, they explained, is how do axons, the thin cellular cables that transmit information in the nervous system, grow? Since about 95% of total protein found in the axon is made in the cell body, it is widely recognized that axonal transport is essential for this process. In parallel, there is a deep interest in developing a better understanding of how growth cone mechanics, at the tip of the axon, modulate the rate and control the direction of axonal elongation.
While these topics lend themselves well to mathematical modeling there has been limited direct interaction between experimentalists and theoreticians. Answering these questions is important for understanding the development of the nervous system, the pathological progression of neurodegenerative diseases such as Alzheimer’s, and for designing novel approaches to promote neuronal regeneration following disease, stroke, or trauma.
Jung: Trying Something New
Johnson’s adviser, Dr. Peter Jung, Distinguished Professor of Physics at Ohio University, has been collaborating with Fenn’s adviser, Dr. Anthony Brown, Professor of Neuroscience at Ohio State University, about the biological mechanisms behind a cellular process called axonal transport, as well as its effects on axonal morphology and neuronal function.
“Tony and I tried something completely new, we paired a M.D.-Ph.D. student from Ohio State University with a physics graduate student at Ohio University to tackle an important problem in contemporary cell biology, namely to determine how teams of molecular protein motors transport cargo through a cell,” explained Jung. “This is a formidable problem, which requires highly time-resolved fluorescent video imaging in a life neuron, image processing, and computational modeling. While the entire team met regularly in Tony’s lab to discuss the progress, Chris and Dan were in charge of the project. Chris and Dan did an amazing job – they worked together extremely well.”
“Chris learned a whole lot about cell biology and life-cell imaging and Dan learned a lot about the power of computational modeling in cell biology,” Jung continued. “It was amazing to see Chris mature to become an independent biological physicist with a solid understanding of cell biology and neuroscience, the experience to collaborate with a biology-lab, and most importantly the experience how to apply modern physics to help solving problems in the life sciences.
Their work together resulted in an added benefit – an invited talk at an international conference at the Mathematical Bioscience Institute at OSU. Just as Chris and Dan worked as a team, they presented their work as a team. They took turns to describe experiments, image processing, and computational modeling. Their presentation was extremely well received – and the advisers were proud.”
Johnson: A Tandem Approach
“My talk was about the connection between neurofilament transportation via molecular motor proteins,” explained Johnson. “Dan and I asked the question “Is neurofilament transport guided by a tug-of-war mechanism between dissimilar motors?” Due to the large overlap between theory and experiment in this project, we were permitted to do a joint presentation where we played ‘tag team’: Dan discussed the experimental procedures, protocols, and experimental results; I explained the methods involved in extracting information from the data for analysis; Dan discussed the biological implications of the analysis which poses a tug-of-war mechanism in filament transport; and then I finished up by introducing the tug-of-war model we are developing. We ended our talk with a joint Q&A session,” he said.
“The workshop was informative — it was quite astonishing really. I got to see so many different perspectives on this topic of research, as well as see the broad span of different levels of expertise that others have to offer in this field. This experience opened my eyes on the seeing the importance of collaboration between the different disciplines.”
Our Ideal Bio-Physical Lab
“My thesis research focuses on cellular communication, specifically dealing with neuronal communication associated with axons of nerve cells—both intracellular (inside the cell) and extracellular (outside the cell). The portion of research I presented at the MBI workshop deals with intracellular transport of neurofilaments within axons,” Johnson continued.
“The collaboration between Dr. Jung’s Lab and Dr. Brown’s lab (OSU) is straightforward: Dr. Brown’s Lab consists of a team of experimental cellular biologists while Dr. Jung’s lab consists of a team of computational biophysicists, and both of us (both teams that is) share common interests in studying the cytoskeleton of nerve cells and the processes involved in axonal transport.
In a scientific study like ours, if we wish to understand the mechanisms behind any system, the individual components of that system need to be isolated and studied one by one. Yet biological systems are inherently one of most complicated and messy systems that exist, and require expertise in essentially all of the natural sciences. To address this challenge, our collaborative team has merged to create an ideal bio-physical science lab.
For a graduate student studying computational biophysics/neuroscience, this is perfect. Theory can only go so far, and at some point we need in-vivo data from the systems we are trying to model. That’s where our team members at OSU come in. Ultimately, we are trying to understand what leads to neuronal dysfunction and disease. Right now we are working on trying to better understand what governs healthy cellular communication. By merging experiment biologists with computational physicists, we can develop models that replicate the behavior of healthy communication within (and among) cells, which may lead to predictions on what leads to the pathogenesis of motor neuron diseases,” Johnson said.
“In the end, the talk went very well and the workshop was a lot of fun…it was quite astonishing really. I got to see so many different perspectives on this topic of research, as well as see the broad span of different levels of expertise that others have to offer in this field. This experience opened my eyes on the seeing the importance of collaborations between different disciplines. Bio-physics really is an interdisciplinary study.”
Read Christopher Johnson’s and Daniel Fenn’s combined abstract.
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