Author: Winston L

Dr. Neunlist visited us on April 2nd, 2019. He earned his PhD in electrophysiology in 1994 at University Louis Pasteur in Strasbourg, France. In his postdoctoral position in the laboratory headed by Michael Scheman in Hannover, Germany, he worked in the field of neurogastroenterology. Since 2007, he has directed a laboratory devoted to the study of enteric nervous system and enteric neuropathies. During his visit, he shared the importance of the enteric nervous system in the gut and some exciting new techniques using optical coherence tomography to image the ENS in the intestine. Finally, he shared some interesting new findings implicating the gut in Parkinson’s disease.

See his work here.Join us! Apr 2 @ 4PM in MSRB3 1125

Re-engineering Rabies Virus

Dr. Wickersham elaborates on his lab’s work regarding the creation of a second-generation rabies virus. This second-generation rabies virus was created through the replacement of the G and L genes of the virus with Cre. This virus was found to be able to spread trans-synaptically, and the survival of cells infected with this virus was greater than cells infected with the first-generation virus. However, this second-generation virus did not come without its limitations. It was not as effective as the first-generation virus and more complex. This led to the creation of the third-generation rabies virus. This virus was created by replacing only the L gene with Cre, as opposed to both the G and L genes. The Wickersham lab proved that this third-generation virus does not kill cells and is able to spread trans-synaptically. Additionally, Wickersham’s lab proved that coating with EnvA also works with this third-generation virus.

See his work here.

Dr. Cheryl Nickerson is a professor at the Biodesign Center for Immunotherapy, Vaccines and Virotherapy at Arizona State University. Her lab studies the effects of biomechanical forces on living cells (microbial and human), how this response is related to normal cellular homeostasis or infectious disease, and its translation to clinical applications. She and her lab have developed several innovative model systems to study these processes including 3-D organotypic models of human tissues that mimic the structure and function of in vivo tissues and their application to study the host-pathogen interaction that leads to infectious disease.

Dr. Cheryl Nickerson’s lab’s aim to bridge the gap between current intestinal models and the real intestine. Her laboratory has pioneered the uses of Rotating Wall Vessels, which can model low fluid shear in mucosal tissues in the intestine. Her past work involved determining if the characteristic of Salmonella Typhimurium would change under low fluid shear conditions as compared to high fluid shear conditions. She also talked about her recent advancement in creating 3D intestinal models, which have been shown to have better tight junctions and specialized epithelial cell types such as M cells and goblet cells. This intestinal model can also differentiate between various Salmonella strains, such as a GI strain and a deadly bloodborne strain, and can model different effects of Salmonella infection on the small intestine and colon. She looks to advance her model by adding commensal microbes and the patient fecal microbiome, as infections occur in these specific environments.

See her work here.

Dr. Allbritton is the Kenan Distinguished Professor and Chair of UNC/NC State Joint Department of Biomedical Engineering. She shared her exciting work focusing on microengineered organ-on-a-chip systems for colon and small intestine.

Speaker: Seongjun Park, Ph.D., Postdoctoral Associate in Dr. Polina Anikeeva’s Bioelectronics Group at Massachusetts Institute of Technology

Title: Bioelectronics for neural engineering

Summary: Dr. Seongjun Park received his Ph.D. in Electrical Engineering and Computer Science from MIT in Dr. Polinia Anikeeva’s lab in June of 2018. His doctoral research, which he has expanded upon in his post-doctoral work, has focused on flexible fiberoptics. In the brain, use of electrodes for long term stimulating and recording has been limited by the intense inflammatory response causing inflammatory cell infiltration and scarring. Dr. Park developed a novel flexible fiberoptic to improve the modulus mismatch between the brain and the electrode material. Using this device, he was able to use optogenetics to probe anxiety behavior associated with the circuit between the ventral hypothalamus and the basolateral amygdala. He also extended his work into the spinal cord. For success in the spinal cord, Dr. Park identified the need for a device that can stretch and deform; so, he engineering a stretchable fiber with excellent light transmission properties. Finally, Dr. Park has sought to further engineering his flexible fiberoptic by using a hydrogel coating. By coupling the hydrogel with the flexible fiberoptic, Dr. Park reduced strain between the device and the brain. Using this device, for the first time in the field, Dr. Park was able to record single unit spikes out to 6 months post-implantation. Dr. Park’s ambition is to be an independent investigator in bioengineering, with the goal of engineering devices to improve human health.

Speaker: David Hildebrand, Ph.D., Postdoctoral Associate in Dr. Winrich Freiwald’s Laboratory of Neural Systems at Rockefeller University

Title: High throughput TEM

Summary: Dr. David Hildebrand received his Ph.D. in Neuroscience from Harvard University in the Engert Laboratory. In his doctoral work, Dr. Hildebrand related anatomy, physiology, and behavior in the zebrafish nervous system. In particular, he used developed electron microscopy techniques to image the zebrafish brain at nanoresolution. Transmission electron microscopy is a fast, high signal to noise ratio, and inexpensive way to obtain high resolution images. However, the tissue processing is extremely challenging—nanometer thin samples must be placed by hand on a clear surface for imaging. Scanning transmission electron microscopy, however, can image with intact samples, but it sacrifices speed, resolution, and signal to noise ratio. Dr. Hildebrand merged the benefits of both systems by engineering a automated serial sections to tape transmission electron microscopy system. In his system, tissue is automatically sectioned and mounted to clear tape for transmission imaging. Using this system, he was able to obtain exquisite images of both the zebrafish brain as well as the mouse gastrointestinal tract.

Speaker: Ian Williamson, Ph.D., Postdoctoral Associate in Dr. Xiling Shen’s and Dr. John Rawls Laboratories at Duke University

Title: Nanofeeding human miniguts

Summary: Dr. Williamson received his Ph.D. in Biomedical Engineering from UNC/NCSU in the laboratory of Dr. Scott Magness. Early in his doctoral work, he was struck by how understudied the intestinal epithelium is. In particular, he was interested in how the microbiome interacts with the epithelial layer. He identified several techniques to better study the epithelial layer with the microbiome intact: culture with bacteria, microinjections of bacteria into organoids, or 2-D culture. Microinjection techniques were limited by the use of conventional technology, so Dr. Williamson developed a system for high throughout injection of fecal microbiome directly into the lumen of organoids. He identified that after injection into the lumen, the organoids live healthily in culture for up to 96 hours. During that time, the number of species in the microbiome increases with minor changes in species representation. Using this system, he further went on to demonstrate that organoids are able to reproducible metabolize fatty acids injected into their lumen. Dr. Williamson hopes to expand upon these techniques to study the gut epithelium in his post doctoral work at Duke University.

Speaker: Meg Younger, Ph.D., Kavli Fellow in Dr. Leslie Vosshall’s Laboratory of Neurogenetics and Behavior at Rockefeller University

Title: Processing human cues in the mosquito brain

Summary: Dr. Meg Younger received her Ph.D. from UCSF studying the homeostatic regulation of neurotransmitter release in the laboratory of Dr. Graeme Davis in 2013. Since joining Dr. Leslie Vosshall’s laboratory for her post-doctoral fellowship, Dr. Younger has focused on studying how mosquitos identify humans by sensory cues. Mosquitos integrate sensory information including body heat, human odor, and carbon dioxide emissions to find a blood meal. The human order code, however, remains unknown. Because mosquitos are not a model system, Dr. Younger began her research by developing a standard reference brain for mosquitoes (mosquitobrains.org). Using this, she identified 50 glomeruli for odor sensation; she targeted 3 specific glomeruli that synapse with sensory neurons from the maxillary palp. Using the CRISPR Q system and calcium imaging, she has been able to identify that the mosquito odorant is quite different that that of other model systems such as drosophila. Some sensory neurons express multiple odorant receptors to synapse on one glomeruli, while other sensory neurons express only one odorant receptor. And, one glomeruli may receive signals from multiple sensory neurons with different receptors. Using this work as a foundation, she hopes to uncover how mosquitos find humans.

Reinventing Bariatric Surgery

Dr. Randy Seeley is the Henry K. Ransom Endowed Professor of Surgery at the University of Michigan School of Medicine. He also serves as the director of the NIH-funded Michigan Nutrition Obesity Research Center (MNORC). His scientific work has focused on the actions of various peripheral hormones in the CNS that serve to regulate food intake, body weight and the levels of circulating fuels. His work has also focused on new treatment strategies for obesity and diabetes. He has published over 310 peer-reviewed articles including articles in Science, Nature, Nature Medicine, Nature Neuroscience, Science Translational Medicine, Cell Metabolism, The Journal of Clinical Investigation and the New England Journal of Medicine. Collectively, this work has been cited more than 28,000 times and Dr. Seeley has a scopus h-index of 82. Dr. Seeley has received numerous awards including the 2009 Outstanding Scientific Achievement Award from the American Diabetes Association. This award is presented to an individual medical researcher under age 45 who has made an outstanding contribution to diabetes research that demonstrates both originality and independence of thought. Dr. Seeley has also served on numerous review panels for the NIH and was Chair of the Integrative Physiology of Obesity and Diabetes review panel and on the Board of Reviewing Editors for Science. He is currently Senior Associate Editor for Diabetes. See his work here.

Will de Lartigue is an Assistant Professor in Pharmacodynamics at the University of Florida. His lab studies the neurobiology of feeding. They are specifically interested in an understudied set of peripheral neurons that make up the sensory arm of the vagus nerve. These neurons form a direct anatomical link between the gut and the brain and provide a rapid neural mechanism for conveying information about the gastrointestinal environment to the brain. Although electrical stimulation of the vagus nerve is proving effective in treating a number of diseases, a lack of tools available to study the role of specific subsets of vagal neurons in physiological and disease states has led to an incomplete understanding of this pathway. They make use of molecular and genetic tools to target, image, and trace projections from subpopulations of sensory vagal neurons that innervate the gut to study the signals that active them and the circuits they recruit. In combination with behavioral, physiologic, and neurochemical techniques we study the role of vagal sensory neurons in the control feeding behaviors.

See more of his work here .

Adult enteric neurogenesis: Implications for gut and brain health and disease

Dr. Subhash Kulkarni, M.S., Ph.D., is an Assistant Professor of Medicine at the Johns Hopkins University School of Medicine. His research focuses on the origin and development of the enteric nervous system (ENS). The ENS is maintained despite significant and continuous insults, and chronic dysmotility can result from dysregulation of the ENS. However, there is significant conflicting data on the stability of the ENS over a lifetime, with research disputing the occurrence of apoptosis and neurogenesis of enteric neurons. Dr. Kulkarni’s laboratory’s research has focused on investigating three central hypotheses: 1) the ENS is maintained by a balance of apoptosis and neurogenesis, 2) ENS turnover contributes to recovery from insult, and 3) issues with the autocorrect mechanisms regulating the ENS can cause adult onset dysmotility. In work published in PNAS in 2017, Dr. Kulkarni and colleagues showed that apoptosis and neurogenesis occur in balance to maintain a steady number of enteric neurons over time. Further, they showed that Nestin+ cells are the enteric neuron precursor cells that proliferate and generate adult neurons, replacing 88% of the adult ENS in two weeks. To address their second hypothesis, Dr. Kulkarni and his laboratory considered the intestinal insult of antibiotics. After exposure to the antibiotic ampicillin, intestinal dysbiosis changes ganglionic diversity, and over time, increased neurogenesis restores neuronal numbers to pre-ampicillin levels in a TLR2 mediated mechanism. Finally, Dr. Kulkarni and colleagues studied how ENS neurogenesis from precursor cells could contribute to disease. Knocking out PTEN in enteric neuron precursor cells caused unchecked proliferation and significantly increased neuronal numbers, size, and whole-gut transit time— an intestinal phenotype that resembled ganglioneuromatosis, a disorder of adult onset dysmotility. Dr. Kulkarni and his lab will continue to study how the ENS originates and develops and how it affects diseases of dysmotility.