The Omics Data Science Lab led by Dr. Jesse Meyer at the Medical College of Wisconsin in Milwaukee seeks postdoctoral fellows or research scientists to spearhead studies in three areas of research focus: 1) Neurodegeneration. We develop iPSC-derived models of neurodegeneration for high throughput multi-omic analysis to discover drugs and enable understanding of neuroprotective pathways. The applicant will have a PhD (or MD with substantial laboratory experience) related to neuroscience or neurobiology. Expertise in Alzheimer’s disease or amyotrophic lateral sclerosis, iPSC-derived neurons, cellular assays, imaging, are desired. 2) Multi-Omics. We develop and apply new mass spectrometry methods to collect quantitative molecular data from biological systems more quickly (Meyer et al., Nature Methods, 2020). The applicant will have a PhD (or MD with substantial laboratory experience) related to analytical chemistry, especially mass spectrometry-based proteomics and/or metabolomics and/or associated bioinformatic skills especially machine learning. The multi-omic analysis methods we develop will be paired with machine learning to understand changes in metabolism associated with disease. 3) Data Science. We develop and apply machine learning methods to biological problems (Meyer et al. JCIM 2019, Overmyer et al. Cell Systems 2021, Dickinson and Meyer bioRxiv 2021). The applicant will have a PhD (or MD with substantial laboratory experience) related to computational biology especially machine learning and deep learning. Expertise in cheminformatics is preferred. Projects relate to chemical effect prediction and automated interpretation of omic data. Applicants must have experience in one of the above focus areas, and interest in learning the other focus areas is desired. The Omics Data Science Lab led by Dr. Jesse Meyer is a basic and translational research group in the Department of Biochemistry at the Medical College of Wisconsin. We have our own mass spectrometer (Orbitrap Exploris 240 with FAIMS) and related support equipment, and access to abundant human samples paired with EHR data through the MCW tissue bank and clinical data warehouse. The Medical College of Wisconsin is the 3rd largest private medical school in the United States and ranks in the top 1/3 of medical schools for NIH funding received. Successful applicants are expected to work independently in a collegial and supportive yet demanding environment. Potential for self-funding is welcome but not essential. Inquiries and applications (including CV, contact info for 2-3 references, and reprints of 2 most significant publications) should be directed to: Jesse G. Meyer, Ph.D. Assistant Professor, Department of Biochemistry, Medical College of Wisconsin jesmeyer@mcw.edu www.jessemeyerlab.com

Despite the profound effects of nutrition and physical activity on human health, our understanding of the molecules mediating the salutary effects of specific foods or activities remains remarkably limited. Here, we share our ongoing studies that use unbiased and high-resolution metabolomics technologies to uncover the molecules and molecular effectors of diet and exercise. We describe how exercise stimulates the production of Lac-Phe, a blood-borne signaling metabolite that suppresses feeding and obesity. Ablation of Lac-Phe biosynthesis in mice increases food intake and obesity after exercise. We also describe the discovery of an orphan metabolite, BHB-Phe. Ketosis-inducible BHB-Phe is a congener of exercise-inducible Lac-Phe, produced in CNDP2+ cells when levels of BHB are high, and functions to lower body weight and adiposity in ketosis. Our data uncover an unexpected and underappreciated signaling role for metabolic fuel derivatives in mediating the cardiometabolic benefits of diet and exercise. These data also suggest that diet and exercise may mediate their physiologic effects on energy balance via a common family of molecules and overlapping signaling pathways.

We are interested in understanding how microbes impact the behavior of host animals. Animal nervous systems likely evolved in environments richly surrounded by microbes, yet the impact of bacteria on nervous system function has been relatively under-studied. A challenge has been to identify systems in which both host and microbe are amenable to genetic manipulation, and which enable high-throughput behavioral screening in response to defined and naturalistic conditions. To accomplish these goals, we use an animal host — the roundworm C. elegans, which feeds on bacteria — in combination with its natural gut microbiome to identify inter-organismal signals driving host-microbe interactions and decision-making. C. elegans has some of the most extensive molecular, neurobiological and genetic tools of any multicellular eukaryote, and, coupled with the ease of gnotobiotic culture in these worms, represents a highly attractive system in which to study microbial influence on host behavior. Using this system, we discovered that commensal bacterial metabolites directly modulate nervous system function of their host. Beneficial gut microbes of the genus Providencia produce the neuromodulator tyramine in the C. elegans intestine. Using a combination of behavioral analysis, neurogenetics, metabolomics and bacterial genetics we established that bacterially produced tyramine is converted to octopamine in C. elegans, which acts directly in sensory neurons to reduce odor aversion and increase sensory preference for Providencia. We think that this type of sensory modulation may increase association of C. elegans with these microbes, increasing availability of this nutrient-rich food source for the worm and its progeny, while facilitating dispersal of the bacteria.