Dr. Jim Vigoreaux
Research in Dr. Jim Vigoreaux's lab focuses on six areas of muscle biology:
(1) The role of myosin binding proteins in defining the structural and mechanical properties of thick filaments, specifically myosin binding protein C (MyBP-C) in vertebrate heart and flightin in invertebrate muscles. This research uses classical and molecular genetic approaches in the fruit fly, Drosophila melanogaster, to uncover protein structure and function relationships, and the effect of mutant proteins on thick filament properties, muscle structure and mechanics, and animal performance. Current projects include: (i) determination of the three dimensional structure of native Drosophila flight muscle thick filaments from wild-type and flightin knock-out flies. (ii) biochemical and structural characterization of the myosin rod interaction with flightin and MyBP-C. (iii) the role of phosphorylation and the effect of mutations on flightin and MyBP-C on the biomechanical properties of native thick filaments.
(2) Role of flight muscle in Drosophila mating song and the effect of muscle mutations in courtship behavior. This work examines the potential interplay between sexual selection and natural selection in the evolution of insect flight muscle.
(3) Molecular evolutionary analysis of muscle proteins and comparative analysis of arthropod muscles. This research combines phylogenetic approaches with analysis of gene expression and morphological properties to gain perspectives on muscle evolution.
(4) Functional and evolutionary analysis of glutactin, an insect basement membrane protein that influences muscle development and contractility, and animal locomotion.
(5) The interaction of genes, nutrition, and exercise in aging flies and the role of muscle in regulating lifespan and healthspan.
(6) Muscle energetics, in particular the combination of computational modeling, nanovolumetric fractionation, and genetic approaches to test for the existence of glycolytic enzyme complexes that channel metabolic intermediates and enhance the production of ATP.
Trainees in the Vigoreaux lab use modern approaches in molecular genetics and proteomics, techniques in protein biochemistry, microscopy (EM, confocal, and AFM), image analysis, cellular biology, and animal behavior analysis (feeding, courtship, locomotory).
Pedro Alvarez Ortiz, Graduate Research Associate (PhD, 2014) - I obtained a BS and MS from the University of Puerto Rico and a PhD in 2014 from the University of Vermont. My PhD thesis focused on the phylogeny and expression patterns of two Drosophila proteins, flightin and glutactin: flightin is a sarcomeric protein essential in the indirect flight muscle while glutactin is an extracellular basement membrane (BM) protein previously shown to surround muscle during embryonic development. Our phylogenetic results from glutactin and flightin revealed that both proteins are taxonomically restricted: glutactin is present only in the Drosophila group whereas flightin is confined to Pancrustacea. The expression pattern of glutactin in the larva revealed that in addition to being a BM protein surrounding the body wall muscles, glutactin is also a muscle protein present in the costameres. Its down-regulation in the muscles of the larva slowed their crawling speed in comparison to controls. In adults, glutactin was detected surrounding direct flight muscle, the abdominal intestinal tract and reproductive system. Its ubiquitous down-regulation revealed that more than 50 percent of the adult flies died during the first two to three days after eclosion, and the surviving adult have reduced lifespans. In addition, the number of embryos laid by females that survived past three days was significantly reduced compared to control females. Result from the expression of flightin in different species of insects revealed that it’s broadly expressed except in those Diptera species that belong to the Schizophora lineage where its expression is limited to the thorax. Moreover, we detected the presence of flightin isoforms in the larva of several species that are different from corresponding flightin isoform detected in the adult. Our studies reveal the important roles that taxonomic restricted proteins play in the organism as their absence and down-regulation result in the loss of features that seems essential for normal life.
Lori Nyland, Research Technician - I have an M.S. in Bioengineering from UVM. In the Vigoreaux lab I have worked on determining thick filament stiffness using atomic force microscopy and currently I am working on determining the 3D high resolution structure of the native relaxed thick filament.
Andrew Mead, Research Associate - I joined the Vigoreaux lab in Spring 2013 after completing my PhD in biology at the University of Pennsylvania, where I worked on gene-based therapies to treat Duchenne Muscular Dystrophy. I am interested in how the balance of energy availability and energy consumption in muscle cells effects body-wide physiological processes relevant to healthspan and lifespan. Ease of genetic manipulation and well-characterized flight muscles make Drosophila melanogaster a powerful model for studying metabolic homeostasis in muscle. I am currently developing methods to test the effects of flight exercise on whole organism physiology.
Lynda Menard - I graduated from WPI in Feb 2008 with a B.S. in biology before moving on to Mass Biologics where I participated in the development of mutant SOD1 Abs. After that I proceeded to Alnylam where my research focused on the utilization of siRNA to enhance the production of desired cell products. I am currently examining the possible functional homology between vertebrate cardiac Myosin Binding Protein-C (cMyBP-C) and invertebrate flightin (FLN) and have utilized atomic force microscopy (AFM) and transmission electron microscopy (TEM) to evaluate thick filament persistence length and sarcomere structure in the indirect flight muscle (IFM) transgenic D. melanogaster models expressing cMyBP-C with and without FLN. I am also examining localization and characterizing binding kinetics of these proteins in the IFM. Other interests include biomimetics and biomaterials, specifically employing alpha-helical coiled-coils such as that found in the light meromyosin (LMM) region of myosin II thick filaments.
Emily Price - I am a first year PhD student in Dr. Vigoreaux's laboratory. I am interested in both applying "big-picture" ecological views to molecular phenomena and in the intersection between physiology and behavior. I also enjoy teaching/science outreach and microscopy.
Ravi Nagori - I am a first year graduate student. Calcium pumps are a major contributor to any cellular system. As such cells have different genes which have the code for different types of calcium pump. My research focuses on the study of these genes of a paramecium under various conditions to elucidate the entire biochemical pathway for calcium pump regulation.
James Contompasis - I am currently an undergraduate student in the Honor’s College from Burlington, Vermont pursuing a B.A. in Biology with a minor in Chemistry. I intend to write an Honors thesis in my senior year based on the research that I do in this lab. I am studying the possibility of functional homology between the myosin rod binding proteins flightin and cardiac Myosin Binding Protein C (cMyBP-C). I am currently doing this by protein quantification of transgenic lines of Drosophila melanogaster. I am also currently involved in a project aimed at determining the role of the mTOR pathway in HMB metabolismstudying C-terminal and N-terminal deletions of flightin.
Campbell Dickson - I am a UVM student currently entering my fourth year of study. I am on track to receive a B.S. in Integrated Biological Sciences, a B.A. in Mathematics, and a minor in Chemistry. My studies focus primarily on methods of mathematically modeling complex biological and chemical systems. I work closely with a number of researchers in Dr. Vigoreaux’s lab to understand the thick filament-associated protein flightin. My part in the research involves dissection of flies and isolation/purification of flightin, 1D SDS-PAGE of thick filament proteins and myosin rod binding proteins to determine binding stoichiometry, and affinity chromatography co-sedimentation assays to determine which amino acid residues of the myosin rod’s light meromyosin (LMM) region are involved with binding flightin and its functional homologue, cardiac Myosin Binding Protein C (cMyBP-C).
Harshal Athalye - I am an undergraduate Honor’s College UVM student currently entering my fourth year of study. I am pursuing a B.A. in Biology with a minor in Chemistry. I am currently working on a project dealing with genetic analysis of flightin function in Drosophila through the method of gel electrophoresis to determine phenotypic differences in different Drosophila lines expressing N-terminal and C-terminal deletions of flightin. I will be transitioning into my senior honors thesis, which deals with functional characterization of a Drosophila transgenic line expressing a Chimeric flightin, and the implications on flight muscle structure and male courtship song.
Clare Martin - I am an undergraduate student entering my final year
Mike McCarthy -
Nathan Gasek - I am going into my third year at UVM. I am pursuing a double major in Biology and Chemistry. With the assistance of the Beckman Scholars program, I am studying the myosin binding protein flightin with the Vigoreaux Laboratory. Specifically, I use an Atomic Force Microscope to measure the effects of flightin mutations on the stiffness and structural characteristics of thick filaments found in the indirect flight muscles of Drosophila. I also assist in protein purification techniques with the laboratory's graduate students.
Shakira Quiñones – I obtained a Masters degree in Biology from the University of Puerto Rico. My current project involved analysis of mating songs from Drosophila flight muscle mutants.
Matt Rosenthal - I am currently engaged in a B.A. Biology Major with Chemistry and Pharmacology as minors. My current lab project is coming to understand how the structural protein Flightin, found exclusively in Drosophila melanogaster’s asynchronous Indirect Flight Muscles (IFM) that provide flight and courtship song, can be both naturally and sexually selected for. Flightin is a 20 kD protein binding in the myosin rod region that is required for maintaining the length of the thick filament during structural development and further more the structural integrity of the IFM. With sequence comparison between 12 species of Drosophila, the protein can be broken down into three different conserved sections providing leading questions of “What is causing the differences in sequence conservation and what evolutionary selection processes are acting on Flightin?” Various truncations to the Flightin protein have been expressed in fly models and tested by several flight and courtship assays as well by protein expression analysis.
Whitney Stevens Sostre - I am from Ponce, Puerto Rico and am an undergraduate student from the University of Puerto Rico at Mayaguez. I was an undergraduate research intern in Dr. Vigoreaux's lab during the summer of 2013. My research interest is primarily Neuroscience and understanding the Drosophila melanogaster model system. My summer research project consisted of optimizing an immunostaining protocol to be performed on dissected indirect flight muscles (IFM) in adult D. melanogaster flies.
Richardo Santana Santini - I am a high school student from San Juan, Puerto Rico and was a summer intern in Dr. Jim Vigoreaux's lab at UVM. My research involved the analysis of crawling speed of larva fed different diets containing nutritional supplements.
Pedro Alvarez-Ortiz (PhD, 2014)
Alexandra Beattie (MS, 2014)
Samya Chakravorty (PhD, 2013)
Michael Previs (PhD, 2010) (Co-mentor)
Byron Barton (PhD, 2007)
Vivek Vishnudas (PhD, 2006)
Joshua Henkin (PhD, 2004)
Gretchen Ayer (MS, 2001)
Jeff Moore (PhD, 1999) (Co-mentor)
Carmen Hernandez (PhD,1998)
Rachel Lacy (2005)
Dominick Lemas (2004)
Matthew Rosenthal (BA, 2014)
Judith Contompasis (BA, 2012)
Veronica Foelber (BS, 2012)
Mathew Wadja (BA, 2011)
Nathan Davis (BA, 2011)
Shawna Guillemette (BS, 2006)
Whitney Stevens Sostre, 2013
Ricardo Santini, 2013
Netsha Santiago, 2012
Maxine Gonzalez, 2012
Karoline Rios, 2012
Lucia Herrera, 2012
Vedran Beganovic, 2011
Nicolle Rosa, 2011
Elizabeth Gutierrez, 2009