Frontiers in MBM: Paul Selvin, March 22

Paul SelvinPaul Selvin, Professor of Biological Physics at Illinois, will lecture on “Live Brain Slices & Neurons at Nanometer-resolution” at 4:00 pm March 22  on ZOOM ONLY.  Shannon Berneche, MBM trainee and PhD candidate, will give an introduction.

The lecture is free and open to the public courtesy of the Miniature Brain Machinery Program.

Abstract:

We have developed a number of techniques that can be used to study neurons, and separately, molecular motors.

In neurons, the AMPA Receptors (AMPARs) are primary receptors that enable a neuron to communicate with another neuron. During learning, the number of AMPAR increases, and likewise, during forgetting the number decreases. During neuropathies, such as Alzheimer’s Disease (AD), the AMPARs inexorably decrease. We are interested in seeing the dynamics and the number of AMPAR both with learning (called Long Term Potentiation, or LTP) and with AD on living brain slices. Because the AMPARs are in the synapses, where the dimensions are < 30 nm or-so, we need to do this with super-resolution.

We have developed several new labelling techniques—using antibodies, fragments of antibodies, new chemical cross-linkers—combined with several new techniques which go by the name of FIONA, STORM, PAINT and MINFLUX. We present the first nanometric resolution of thick (~30 mm) and living brain slices where we see nanostructures of AMPAR. We also present the first live measurement of LTP in dissociated neurons which quantitatively measures the increase in two isoforms (GluA1 and GluA2) of AMPAR.

Bio:

Paul Selvin earned a PhD in Physics (informally specializing in biophysics) from the University of California, Berkeley, in 1990. His postdoctoral training first focused on developing a new type of fluorescence resonance energy transfer (FRET) based on lanthanides, called luminescence resonance energy transfer (LRET). He then studied single molecule fluorescence—the first measurement of FRET between a single donor and single acceptor (Ha, 1996, PNAS).

After joining the Department of Physics at the University of Illinois in 1997, his interest has turned to molecular motors — proteins whose job is moving cargoes around the cell. His research found that from the biggest motor, Myosin V, (Yildiz, 2003, Science) to the smallest motor, kinesin, (Yildiz, 2004, Science), to one in between (Myosin VI), (Yildiz, 2004, J.Biol.Chem.), the motors all moved in a hand-over-hand, or walking, fashion. This discovery won the award as one of the ten most significant advances in science for 2003, as judged by Science magazine.

Selvin is now combing Fluorescence Imaging with One-Nanometer Accuracy (FIONA), the technique he has devloped, with optical traps (holding particles with light) in vivo, to see how many motors are causing such large velocities. His future plans call for measurements in situ, for example, in Planaria and in C. Elegans, to test how these motors act in “real life.”

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