Submitted by Joe Napoli on
Project Title: Muscle function in a mouse model of muscle degeneration.
Starting Semester: Autumn 2019
Project Duration: 1 (One to 4 semesters)
Number of Undergrad Research Positions Available: 2
Project Description:
The worldwide epidemic of metabolic disorders calls for effective strategies for prevention and treatment. Evidence from research laboratories and clinical studies show that overweight and obesity in humans develops from changes in energy and micronutrient metabolism, and cause further irreversible perturbations in energy metabolism leading to diabetes, cancer, neurodegenerative disorders, and other chronic diseases. The Napoli laboratory studies the role of vitamin A metabolism in regulating energy metabolism. This particular SPUR project focuses on regulation of vitamin A metabolism in muscle and its role in regulating energy metabolism.
We are using genetically modified mouse models, one of which is abatement of retinol dehydrogenase 10 (Rdh10). Rdh10 catalyzes the rate-limiting reaction that converts vitamin A (retinol) into all-trans-retinoic acid (RA), the active form of vitamin A. RA activates nuclear receptors and regulates the expression of >500 genes. Results from our laboratory showed that the deletion of Rdh10 decreases RA level in tissues, promoting obesity and dysfunctional metabolism and mitochondrial function, classic symptoms of type II diabetes.
Our preliminary show that muscle from Rdh10-ablated mice accumulate more triacylglycerol and glycogen compared to the wild type (WT) littermates. This affects muscle function. Run-to-exhaustion endurance tests indicate that male ablated mice have lower endurance than WT, whereas females showed the opposite phenotype. Current studies investigate the role of Rdh10 in muscle, focusing on the mechanism of differentiation from satellite cells, and fatty acid and glucose metabolism. During the 2019 fall semester, a postdoc researcher in our lab, Yaxin Zhao, will use this mouse model to continue studing running behavior of Rdh10-KO and WT, relating the results to energy use, using ex vivo lipolysis and glycolysis assays in muscle. Also, we will measure RA and sex steroid hormones, to address the sex-specific phenotypes. From our previous muscle satellite cells in primary culture, we found that differentiated myotubes from the Rdh10-KO mice showed decreased lipolysis protein expression.
Role of Undergraduate Researcher(s):
Interested students will have an excellent opportunity for hands-on training in basic techniques of histology, immunocytochemistry, molecular biology and cell culture, as well as mouse colony management. Students will assist a senior lab member in mouse colony maintenance, muscle tissue collection, primary cell culture, differentiation procedures and retinoid assays. Depending on ability, hands-on experience in protein expression techniques will be available. Students will work under close supervision of the senior lab member, and will be expected to keep a detailed lab journal regarding experiments, read research articles and attend lab discussions.
Qualifications of Undergraduate Researcher(s):
Applicant should be familiar with fundamentals of chemistry, biochemistry, molecular biology and genetics, and show strong interest and responsibility in metabolic research. Previous experience in biology and chemistry laboratory in classroom settings is required. Ability to follow detailed protocols, pay close attention to experimental details, and learn quickly is necessary. Critical thinking and independent work is fostered and encouraged in our laboratory. Ability to work with live animals is essential: comprehensive training will be provided.
Interested students will have an excellent opportunity for hands-on training in basic techniques of histology, immunocytochemistry, molecular biology and cell culture, as well as mouse colony management. Students will assist a senior lab member in mouse colony maintenance, muscle tissue collection, primary cell culture, differentiation procedures and retinoid assays. Depending on ability, hands-on experience in protein expression techniques will be available. Students will work under close supervision of the senior lab member, and will be expected to keep a detailed lab journal regarding experiments, read research articles and attend lab discussions.
Applicant should be familiar with fundamentals of chemistry, biochemistry, molecular biology and genetics, and show strong interest and responsibility in metabolic research. Previous experience in biology and chemistry laboratory in classroom settings is required. Ability to follow detailed protocols, pay close attention to experimental details, and learn quickly is necessary. Critical thinking and independent work is fostered and encouraged in our laboratory. Ability to work with live animals is essential: comprehensive training will be provided.