Changhan David Lee, Ph.D.
Leonard Davis School of Gerontology
University of Southern California
USC Norris Comprehensive Cancer Center
USC Research Center for Liver Diseases

ABSTRACT
Cellular homeostasis is coordinated through communication between mitochondria and the nucleus, organelles that each possess their own genomes. Whereas the mitochondrial genome is regulated by factors encoded in the nucleus, the nuclear genome is currently not known to be actively controlled by factors encoded in the mitochondrial DNA. We previously identified a peptide encoded in the mitochondrial DNA, named MOTS-c (mitochondrial open-reading-frame of the twelve S rRNA -c). MOTS-c regulates insulin sensitivity and metabolic homeostasis in an AMPK- and SIRT1-dependent manner. Our recent studies show that MOTS-c rapidly and dynamically translocates to the nucleus to regulate the nuclear genome in response to cellular stress. Within the nucleus, MOTS-c interacts with stress-responsive transcription factors and can bind to chromatin to regulate a range of adaptive gene expression. In mice, MOTS-c expression is age- and tissue-dependent. Further, MOTS-c treatment reversed age-dependent insulin resistance and significantly improved physical capacity and metabolic homeostasis in aged mice and had a considerable impact on lifespan. In humans, a centenarian-related haplogroup in a Japanese population is linked to functional MOTS-c residue variant. Our data suggest the integration of mitochondrial and the nucleus at the genetic level and that the close intergenomic communication regulates cellular homeostasis and aging.

Host: Young Jang

Ryan Hunter, Ph.D.
Department of Microbiology and Immunology
University of Minnesota

The cystic fibrosis airways harbor complex and dynamic microbial communities whose interactions with one another and the host are recognized as major players in pulmonary decline.  However, details of their in situ physiology are lacking relative to their behavior on the lab bench.  This seminar will focus on two vignettes that address the spatial and temporal in situ dynamics of CF lung microbiota. The first describes a metabolic labeling approach that, when coupled with fluorescent imaging, flow cytometry and genomic approaches, can differentiate actively growing cells from those that are dormant/dead and reveal their taxonomic identities. The second will focus on the role of mucins as a nutrient source for pathogen growth in the lower airways. Specifically, we have revealed a potential role for oral-derived anaerobic bacteria, most commonly thought of as “commensal” flora, in the degradation of respiratory mucins. Mucin-derived metabolites generated through this process can then stimulate the growth and pathogenicity of Pseudomonas aeruginosa and other canonical lung pathogens. This cross-feeding relationship will be discussed in the context of lung disease establishment and progression, and its implications for medical management. 

Marta Wayne, Ph.D.
Department of Biology
University of Florida

Charles F. Baer, Ph.D.
Department of Biology
University of Florida Genetics Institute

Abstract
Understanding the relative contributions of the different evolutionary forces to phenotypic evolution is a central mission of population and quantitative genetics.  As a starting point, it is important to isolate the contributions of mutation from the other forces, because mutation can never be "turned off".  A Mutation Accumulation (MA) experiment provides a way to quantify the cumulative effects of mutation in the (near) absence of natural selection.  Then, comparison of the properties of genetic variation introduced by mutation to those of the standing genetic variation within and/or between populations provides insight into what natural selection does or does not want.  

We use data from a set of C. elegans MA lines to address two fundamental questions in evolution.  First, we quantify the amount of mutational input into the mutational process itself.  We find that the genome-wide mutation rate evolves significantly upward over a few hundred generations of relaxed natural selection.  Second, we compare two independent measures of selection acting on new spontaneous mutations, one of which is conceptually airtight but of limited utility, the other of which is conceptually suspect but of broad utility (and widely applied).  Happily (or coincidentally), the two measures agree with within a factor of two.  We further show that new spontaneous mutations interact synergistically, potentially explaining why we have not Died 100 Times Over.  Finally, we show that the base-substitution spectrum of experimentally accumulated mutations differs significantly from the spectrum of standing rare variants.  That discrepancy means either (a) that natural selection skews the spectrum, or (b) mutations accumulated in the lab do not faithfully reflect the natural spectrum.  We increasingly suspect the latter.

Host: Soojin Yi, Ph.D.

Host: Francesca Storici

Turgay Akay, PhD
Department of Medical Neuroscience
Dalhousie University

Abstract
To generate locomotor behavior, the nervous system must precisely regulate the timing and the strength (locomotor pattern) of multiple flexor and extensor muscle contractions controlling movement at the three joints of the hindlimb. These locomotor patterns are generated by the combined actions of a network of interconnected interneurons within the spinal cord (the central pattern generator) and sensory feedback from the periphery, but how these two components are integrated and collectively act to control movement remain obscure. Using an interdisciplinary approach including mouse genetics, in vivo electrophysiology, motion analysis, and computational methods, I will discuss recent findings in my laboratory addressing the role of proprioceptive sensory feedback in locomotor pattern generation.

About the Speaker
Turgay Akay completed an undergraduate degree in fisheries engineering at Süleyman Demirel University in Turkey. His interest in animal behaviour led him back to Germany, where he was born, to pursue a diploma degree in biology at the University of Bielefeld and a PhD at the University of Cologne’s Institute for Zoology. His PhD thesis addressed the role of sensory feedback in interjoint coordination in insect walking. Upon completing his PhD in 2002, Dr. Akay re-located to North America. Following postdoctoral stints at the University of Pennsylvania with Dr. Michael Nusbaum and University of Alberta with Dr. Keir Pearson, Dr. Akay made the move to Columbia University, where he worked with Dr. Tom Jessell and later became an associate research scientist at Columbia’s Center for Motor Neuron Biology and Disease. Already a long-time collaborator with Dalhousie’s motor neuron researchers, Dr. Akay made the move to Halifax in 2014 to join the Department of Medical Neuroscience as an Assistant Professor.

Physiology Brownbag Seminars
The Physiology Group in the School of Biological Sciences hosts Brownbag Lunchtime Seminars twice a month on Wednesdays at noon in room 1253 of the Applied Physiology Building located at 555 14th Street NW, Atlanta, GA 30318. You are welcome to bring a lunch and join us as we ruminate with us on topics in Physiology! A full listing of seminars can be found at http://pwp.gatech.edu/bmmc/physiology-brownbag-seminars-spring-2019/.

Host: Boris I. Prilutsky, Ph.D.