Posdoctoral position at the Translational Research Institute for Metabolism and Diabetes in Orlando, Florida
The Translational Research Institute for Metabolism and Diabetes is looking for a highly motivated postdoctoral fellow to join the Exercise and Bioenergetics Program at the Translational Research Institute for Metabolism and Diabetes (TRI-MD) in Orlando, Florida. This is a unique opportunity for a candidate with a strong molecular and cell biology background to train in a clinical-translational research environment. Our team is focused on unraveling mechanisms regulating skeletal muscle and adipose tissue bioenergetics and metabolism in the context of aging and disease. We are also particularly interested in the impact of exercise on muscle, adipose, and energy expenditure. The research will aim to translate clinical findings and observations into molecular and cellular mechanisms employing multiple experimental approaches including cell culture, common molecular biology techniques, mitochondrial energetic measurements (Oroboros, Seahorse), and various -omic platforms (RNA-seq, ATAC-seq, ChIP-seq, metabolomics, lipidomics). There will be an opportunity to work with clinical samples, e.g., muscle, adipose tissue and blood) from patients and study participants as well as perform high caliber translational research in a clinical research environment. The ideal candidate will have strong molecular and cell biology training. Additional experience in skeletal muscle and/or adipose tissue biology is a plus.
The TRI-MD is a 54,000 square foot research facility featuring 2 whole-room calorimeters, an 11-room overnight clinical research unit, a 3T MRI, and biorepository. Our Exercise and Bioenergetics Laboratory includes a full training facility with strength and aerobic equipment, testing facility for maximal/submaximal exercise testing and a full wet laboratory including capabilities for cell culture, flow cytometry, single cell analyses, mitochondrial energetics, and histology. Multiple cores including a CLIA-certified laboratory, research imaging, and metabolomics are available to support our research mission.
Specific Aims
A low exercise capacity is an important risk factor for all-cause morbidity and mortality. Skeletal muscle is a critical component of exercise capacity through its ability to generate ATP via mitochondrial substrate oxidation and subsequent muscle contractions. Life-long aerobic exercise training is associated with improved skeletal muscle mitochondrial function which increases exercise capacity, improves whole-body insulin sensitivity and reduces the risk for metabolic disease (e.g. type 2 diabetes, obesity). Relatively short-term (weeks) training induces improvements in these same parameters but depends on the mode, volume and duration of exercise. A critical component of skeletal muscle plasticity are nascent myogenic progenitor cells (satellite cells) as they contribute their myonuclei to existing fibers or fuse to form new fibers. Meager evidence suggests that these satellite cells are “imprinted” by lifestyle interventions in a manner which confers subsequent metabolic adaptations through proliferation and self‐renewal, which in turn provides epigenetic modifications to daughter populations. Satellite cells also offer a novel in-vitro model for cell-autonomous information on exercise-induced changes that are innate (i.e. retained in culture) and intrinsic to skeletal muscle itself. The proposed studies will fill a gap in our knowledge and directly assess the ability of short-term and life-long exercise training to imprint myogenic progenitor cells with metabolic properties through epigenetic modifications.
The NIH Common Fund project “Molecular Transducers of Physical Activity Consortium (MoTrPAC)” is a large-scale discovery study designed to understand the molecular responses to 3 months of aerobic (AT) and resistance exercise (RT) training compared to life-long trainers (athletes) using blood, muscle and adipose. A secondary goal of MoTrPAC is to create a tissue repository. The primary goal of this proposal is to leverage MoTrPAC and determine the distinct abilities of short-termand life-long AT and RT to imprint key myocellular metabolic parameters (insulin sensitivity, mitochondrial function) through epigenetic regulation (DNA methylation, RNA expressions) of genes in skeletal muscle progenitor cells. Our secondary goal is to establish a human primary skeletal muscle cell culture (HSkMC) repository that can be utilized for future mechanistic interrogations of targets identified in the parent study, as well as novel investigations beyond MoTrPAC.
The muscle microenvironment differs with AT vs. RT. Therefore, the magnitude and nature of changes in the satellite cells may also differ with training mode and inform subsequent exercise prescriptions aimed at optimizing health benefits. We hypothesize that short-term training will imprint metabolic properties of skeletal muscle progenitor cells through epigenetic regulation of key exercise-response genes that will differ by training modality.To test this hypothesis, we will establish HSkMC from 325 individuals (AT, RT, control groups) before and following 3 months of intervention and 75 athletes (AT and RT) and assess insulin action (insulin-stimulated glycogen synthesis, insulin signal transduction), mitochondrial function (O2 consumption using carbohydrate and fatty acid substrates), as well as integrate global DNA methylation and RNA expressions to identify relevant exercise targets for cause-and-effect studies. Ours will be the first study to comprehensively link potential molecular transducers of changes in metabolic function that are imprinted in myogenic progenitor cells (HSkMC) by exercise training.
Aim 1: Determine the distinct abilities of short-term and life-long AT and RT to imprint distinct myocellular metabolic properties (insulin sensitivity, mitochondrial function) through epigenetic regulation of key exercise-responsive genes. Expected result: Short-term training will improve insulin sensitivity and mitochondrial function in HSkMC and be more robust in life-long exercisers. Changes in DNA methylation and RNA expression profiles will segregate by mode and display similar patterns in short-term and life-long exercisers. Genetic manipulation in vitro will validate targets identified through epigenetic analyses.
Aim 2: Create an HSkMC repository. The relatively small muscle samples (~125 mg) obtained in the parent project will be largely consumed, leaving little material for the MoTrPAC repository mission. We propose to generate a meaningful repository of muscle-derived samples to supplement the repository that: 1) retain metabolic characteristics of the donor and 2) have been imprinted by exercise training (Aim 1).
Findings from the proposed studies will provide unprecedented mechanistic insight into the ability of exercise training to confer a “metabolic memory” through epigenetic modifications. Adding HSkMC to the MoTrPAC parent repository will also greatly enhance the discovery potential of MoTrPAC, as well as provide a means to study skeletal muscle metabolism in viable intact cells.
Application
You can get more information about the position or apply for the job by contacting Lauren Sparks at Lauren.Sparks@adventhealth.com