Thomas M Duncan, PhD

Thomas M Duncan, PhD
Appointed 05/23/91
4219 Weiskotten Hall
766 Irving Ave.
Syracuse, NY 13210
315 464-8711

Current Appointments

Hospital Campus

  • Downtown

Research Programs and Affiliations

  • Biochemistry and Molecular Biology
  • Biomedical Sciences Program

Education & Fellowships

  • Fellowship: Vanderbilt University, 1990, Biochemistry & Molecular Biology
  • PhD: University of Rochester School of Medicine and Dentistry, 1986, Biochemistry

Research Interests

  • Bioenergetics, enzymology, structural biology, membrane protein function.

Publications

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Research Abstract

My research focuses on the structure and function of the ATP synthase - an energy-coupling enzyme complex that is critical to the energy metabolism of most living things. The ATP synthase is located on the inner cell membrane of bacteria, the inner mitochondrial membrane of eukaryotes and on the thylakoid membrane of plant chloroplasts. In the terminal step of oxidative- and photo-phosphorylation, it extracts energy from a transmembrane, electrochemical gradient of protons to drive the synthesis of most cellular ATP.

Background

The ATP synthase consists of two sub-complexes with distinct but coupled functions. The F0complex spans the membrane bilayer and transports protons. F1 is a peripheral complex that extends into the aqueous phase and contains three catalytic nucleotide binding sites for ATP synthesis (one visible in cartoon). carton F0 and F1 are coupled through two stalk-like connections of subunits, a central rotor shaft and a peripheral stator. My earlier studies with Richard Cross provided key initial evidence that energy coupling by the ATP synthase involves

  1. rotation of the central shaft within F1 to coordinate the actions of three cooperative, alternating catalytic nucleotide sites, and
  2. rotation of subunits within F0 during energy-driven proton transport.

Remarkably, energy coupling by the ATP synthase is very efficient and reversible: respiration-driven proton transport through F0 can drive net synthesis of ATP, but net hydrolysis of ATP can also be used to drive proton transport in the opposite direction, thereby generating a transmembrane, electrochemical proton gradient.

Experimental system

Our research primarily uses the bacterial ATP synthase from Escherichia coli, which provides a simple yet powerful model system for structure/function studies of this rotary motor enzyme. The E. coli system provides straightforward genetic screening and engineering of the ATP synthase, and also allows large-scale purification of F0F1 and isolated F1 for biochemical studies.

Current projects

  1. Determine high-resolution structures of E. coli F1 and F0F1 by X-ray crystallography. A collaboration with Dr. Gino Cingolani, an experienced protein crystallographer (now at Thomas Jefferson Univ., Philadelphia).
  2. Determine how the rotor-associated epsilon subunit regulates activity of E. coli F1, and how epsilon may respond to changes in the electrochemical proton gradient to regulate the activty of membrane-bound E. coli F0F1.
  3. Engineer specific cysteines into different subunits of F0F1 for fluorescent labeling and assays of functional subunit rotation by single-particle fluorescence resonance energy transfer (sp-FRET). A preliminary collaboration with single-molecule microscopist, Dr. Michael Börsch (Physics Institute, University of Stuttgart, Germany).

 

Faculty Profile Shortcut: http://www.upstate.edu/faculty/duncant
Eric Wohlford

Eric Wohlford

Eric Wohlford received a 2012 travel award from the American Society of Tropical Medicine and Hygiene and spent two months in Kenya working in the lab of Rosemary Rochford, PhD, professor and chair of Upstate’s Department of Microbiology & Immunology. Eric studied the effects of malaria on B cells (producers of antibodies that fight infection) and Epstein-Barr Virus infection in the region. “Tropical medicine is unique, in that small, focused improvements in patient care make dramatic improvements in the well-being of patients,” he said.

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Download the MD/PhD 2013-14 Brochure. PDF document