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Frederick Sigworth, PhD

Professor of Cellular and Molecular Physiology and of Biomedical Engineering and of Molecular Biophysics and Biochemistry
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Contact Info

Cellular & Molecular Physiology

PO Box 208026, 333 Cedar Street

New Haven, CT 06520-8026

United States

About

Titles

Professor of Cellular and Molecular Physiology and of Biomedical Engineering and of Molecular Biophysics and Biochemistry

Biography

Fred Sigworth studied applied physics at Caltech and was a graduate student at Yale, working in the neuroscience laboratory of Charles F. Stevens. He received the PhD in physiology from Yale in 1979 and was a postdoc in the laboratory of Erwin Neher in Göttingen, Germany where he was a co-developer of patch-clamp techniques for single-channel electrophysiology. He returned to Yale as a faculty member at Yale in 1984. His current research is in the structural biology of ion-channel proteins, making use of novel cryo-EM methods. "How do I see the scientific enterprise? An old book puts it this way: one generation commends God's works to another. It is a great privilege to unravel the workings of ion channels, and to pass on the excitement about these molecular machines to students, colleagues and anyone else who will listen!"

Appointments

Other Departments & Organizations

Education & Training

Research Associate
Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. (1984)
Post-Doctoral Fellow
Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. (1981)
PhD
Yale University (1979)

Research

Overview

My research work centers on the structure and function of ion channels, which are membrane proteins that selectively control the passage of ions across cell membranes. The activity of ion channels is central to very many physiological processes, including synaptic transmission and impulse propagation in the nervous system, the control of cardiac function and vascular resistance, salt and water transport in epithelia, and the control of hormone secretion.

Central to the understanding of ion channel function is the characterization of the stochastic 'gating' behavior of single channels. We are particularly interested in the 'voltage sensor' of voltage-gated potassium channels, and how it couples the transmembrane potential to channel gating. Towards an understanding of this protein structure, we are pursuing studies using electron cryo-microscopy (cryo-EM) of voltage-gated channel proteins. Electron microscopes have sufficient resolution to provide atomic-detail images, but radiation damage by the electron beam precludes structure determination from a single molecule. Instead, images from many individual protein molecules must be combined to yield even low-resolution structural information. Working with potassium channels reconstituted into lipid vesicles, we use novel specimen substrates and single-particle image processing methods to obtain the three-dimensional structure of these proteins in their various states.

The process of obtaining 3D protein structures from electron micrographs is a very interesting mathematical problem. We are pursuing new approaches to make this process more reliable and able to work on smaller protein particles (like ion channels) than those investigated in the past.


Medical Subject Headings (MeSH)

Biomedical Engineering; Electrophysiology; Ion Channels; Microscopy, Electron; Patch-Clamp Techniques; Physiology; Potassium Channels; Potassium Channels, Voltage-Gated; Sodium Channels; Voltage-Gated Sodium Channels; Xenopus

Research at a Glance

Yale Co-Authors

Frequent collaborators of Frederick Sigworth's published research.

Publications

2016

2013

2010

2009

2008

2007

2006

2002

Academic Achievements & Community Involvement

  • honor

    Fellow

  • honor

    Member

  • honor

    Bohmfalk Teaching Prize

  • honor

    K. C. Cole Award

  • honor

    Yale Science and Engineering Award

Get In Touch

Contacts

Mailing Address

Cellular & Molecular Physiology

PO Box 208026, 333 Cedar Street

New Haven, CT 06520-8026

United States

Locations

  • Sterling Hall of Medicine, B-Wing

    Academic Office

    333 Cedar Street, Ste BE25A

    New Haven, CT 06510

    Business Office

    203.785.2989