Physiology and Biophysics

Seminars

Nov
17
Thu
2016
Lamport Lecture – Robert Lefkowitz @ HSB T-625
Nov 17 @ 4:00 pm – 5:00 pm

“Seven Transmembrane Receptors”

Robert J. Lefkowitz, MD

James B. Duke Professor of Medicine

Investigator, Howard Hughes Medical Institute

Duke University Medical Center

Seven transmembrane receptors (7TMRs), also known as G protein coupled receptors (GPCRs) represent by far the largest, most versatile, and most ubiquitous of the several families of plasma membrane receptors. They regulate virtually all known physiological processes in humans. As recently as 40 years ago, the very existence of cellular receptors for drugs and hormones was highly controversial, and there was essentially no direct means of studying these putative molecules. Today, the family of GPCRs is known to number approximately 1,000, and crystal structures have recently been solved of approximately 25 members of the family and even of a receptor-G protein complex. In my lecture, I will briefly review how the field has evolved over the past 40 years, hanging some of the story on my own research throughout this period. Then I will discuss recent developments in the field, which are changing our concepts of how the receptors function and are regulated in fundamental ways. These include the duality of signaling through G-proteins and β-arrestins; the development of “biased ligands”; and the possibility of leveraging this new mechanistic and molecular information to develop new classes of therapeutic agents. Finally, I will discuss recent biophysical and structural studies of receptor-barrestin interactions.

Apr
6
Thu
2017
2017 Hille Lecture – Thomas Schwarz @ Foege Auditorium
Apr 6 @ 4:00 pm – 5:00 pm

Moving and Removing Axonal Mitochondria

Thomas L. Schwarz, PhD
Professor Neurology
F.M. Kirby Center for Neurobiology
Children’s Hospital, Boston
and Dept. of Neurobiology, Harvard Medical School

Time: 4:00PM

Location: Foege Auditorium, GNOM S060

seminar abstract: Mitochondria are dynamic organelles.  In every cell they move and undergo fission and fusion.  Their distribution and associations with the cytoskeleton change in response to many signals, including the mitotic cell cycle.  In addition, because neurons look like no other cell in the organism, with axons of up to a meter in humans, mitochondrial motility is particularly crucial to the survival of the neuron. The neuron also needs to clear away damaged mitochondria efficiently wherever in the cell they may arise.  Not surprisingly then, defects in the transport machinery of neurons and in their mechanisms for removing damaged mitochondria have been linked to several neurodegenerative diseases, including ALS and Parkinson’s disease.  This talk will present the evidence for a motor/adaptor complex that is responsible for and regulates the movement of mitochondria and will discuss how that movement is regulated by the cell cycle, Ca++, and glucose.  We will look at the operation of two proteins PINK1 and Parkin that are mutated in forms of Parkinson’s disease and examine how these proteins operate in axons to clear away damaged mitochondria that might otherwise compromise the health of the cell.  Particularly in the case of mitophagy, we will consider the special challenges posed for neurons by their extended geometry and the difficulty of having a PINK1-dependent pathway operating far from the soma.

 

Jun
20
Tue
2017
2017 Crill Lecture – William Bialek @ D-209 HSB
Jun 20 @ 4:00 pm – 5:00 pm

Thinking about a thousand neurons

William Bialek
John Archibald Wheeler/Battelle Professor in Physics
Princeton University