Unless otherwise noted, lectures will be held the second Tuesday of each month at 4:00PM in Room 5235/5275 MSC.
September 11th - Determination of the Quaternary Structure of Transporters and Receptors in Living Cells Using FRET and Optical Micro-Spectroscopy
This talk will review our recent advances in Förster Resonace Energy Transfer (FRET) theory and technology that led to the advent of a method for determination of the quaternary structure of protein complexes in living cells. The presentation will describe a spectral-FRET method, which relies on a two-photon microscope with spectral resolution (called Optical Micro-Spectroscopic system, or OptiMiS) and a simple theory of FRET in systems of donors and acceptors to determine the association stoichiometry and configuration of protein complexes (i.e., quaternary structure) in living cells. The talk will conclude with an overview of our results obtained from studies of oligomeric complexes of several G protein-coupled receptors (GPCRs) and transporters in living cells.
October 9th - Illuminating the Ca2+ Triggering of Vesicle Fusion Kinetics at the Calyx of Held Synapse
Ca2+ triggered neurotransmitter release is essential for synaptic function. I am interested in understanding the transient, complex Ca2+ signaling at presynaptic active zones and its impact to the synaptic kinetics at cellular and molecular levels. I will discuss how the combined electrophysiology and optical methods (including the caged compounds photolysis and the super-resolution imaging) facilitate our study at central synapses.
November 13th - Visualizing Retroviral Assembly and Cell-to-Cell Transmission
The spread of viral infection requires a directional flow of genetic information from an infected cell to an uninfected target cell. Many viruses spread as cell-free virions. However, the spread of infection can be orders of magnitude more efficient when viruses can coordinate the processes of assembly and entry at sites of physical cell-cell contact. We have adopted live cell imaging approaches to explore the mechanisms by which retroviruses including the murine leukemia virus and human immunodeficiency virus type 1 (HIV-1) undergo efficient virion assembly and cell-cell transmission. Our ability to visualize these processes has revealed dramatic new details of how these viruses have adapted to hijack their cellular hosts.
December 11th - Optogenetics, Robotic Electrophysiology, and Other Neural Circuit Tools
The brain is a complex, densely wired circuit made out of heterogeneous cells, which vary in their shapes, molecular composition, and patterns of connectivity. In order to help discover how neural circuits implement brain functions, and how these computations go awry in brain disorders, we invent technologies to enable the scalable, systematic observation and control of biological structures and processes in the living brain. We have developed genetically-encoded reagents that, when expressed in specific neuron types in the nervous system, enable their electrical activities to be precisely driven or silenced in response to millisecond timescale pulses of light. I will give an overview of these “optogenetic” tools, adapted from natural photosensory and photosynthetic proteins, and discuss new tools we are developing, including molecules with novel color sensitivities and other unique capabilities. We have developed microfabricated hardware to enable complex and distributed neural circuits to be controlled and observed in a fully 3-D fashion, as well as robots that can automatically record neurons intracellularly and integratively in live brain. These tools are in widespread use to enable systematic analysis of neural circuit functions, and are also opening up new frontiers on the understanding and treatment of brain disorders.
February 12th - Lighting the Fire: Optical Approaches for Studying Ion Channels and Electrical Activity
Information processing in the human brain involves a combination of electrical and chemical signaling pathways. Ion channels are the elementary molecular units that play a central role in generation and propagation of both electrical and chemical signals. To understand how the brain works, we have developed optical tools to study the gating mechanisms of ion channels and their emergent electrical activity in neuronal circuits. In my presentation, I will provide an overview of these optical approaches which have led to a new understanding of biological transistors and neural circuits.
March 12th - Computational Optics – Seeing Around Corners and Through Turbid Media
Imaging is the process of collecting information about a scene and arranging
it in a way that is easily interpreted by the human brain. Optical
imaging in particular has proven to be a powerful method to understand diverse
phenomena from the cytoarchitecture of a cell, materials properties, to
cancer invasion. The last twenty years have seen great advances in optical
imaging with the ability to monitor biological phenomena with unprecedented
resolution and specificity all while maintaining viability and biological
relevance. These high-resolution imaging modalities, which are increasingly
functionally multi-parametric, rely heavily on computational approaches. In
fact, the computational technology and imaging optics should be thought of as
a tightly interwoven system. Computers and advanced electronics are required
for digital capture, visualization and proper data interpretation, but until
now some of the most crucial computational steps of image formation are still
performed by the optics of the imaging system.
The goal of my research is to develop new ways of detection combined with novel computational processing to create and enhance imaging methods and apply them as diagnostic tools in biology and medicine.
April 9th - Optical Interrogation of Large Scale Biological Neural Networks Via Optogenetics
Traditionally, neuropsychiatric disorders have been treated based on the chemical imbalance paradigm, which assumes that any mental disorder is caused by some abnormality in the concentration of chemicals and/or neurotransmitters in the central nervous system. However, there is tremendous interest in going beyond the chemical imbalance paradigm and treating mental diseases by speaking the electrical language of neurons, the so-called interventional psychiatry. Deep-brain and transcranial magnetic stimulation are examples of this approach, in which cellular signaling is manipulated in neural subpopulations to alter network’s collective responses. Despite some exciting results reported, most interventional therapeutic procedures lack specific cell-type targeting strategies and potentially cause serious side effects. There is significant evidence that specific cell-types play crucial roles in several mental disorders. Few cell-type targeted neuromodulation modalities have been introduced to address this challenge. In a very promising approach known as optogenetics, a family of light-gated microbial opsins are developed that function as selective cation channels, and anion pumps, which are expressed in genetically targeted neurons. Once expressed in a neuron, the activity of the cell can be increased or suppressed, with millisecond temporal accuracy, by exposing the cell to light with appropriate wavelengths.
Recent studies have firmly proved that optogenetics has significant potential to open new horizons in neuroscience and brain studies since: specific cell-type targeting can be achieved in optogenetics by using appropriate promoters; bidirectional control of cellular activities are feasible in optogenetics, and high-resolution stimulation patterns can be produced by exploiting the inherent parallelism of optics. Several major applications of optogenetic neuromodulation include: Cracking neural codes, Interrogating neural circuits, Generating reversible models of neurological diseases, and developing efficient therapeutic treatments for psychiatric disorders. Optogenetics has provided a remarkably powerful tool to investigate brain dynamics and communicate with its biological neural networks. Our research is focused on development of new technologies and implementation of novel optoelectronic instrumentation to optically modulate and monitor brain dynamics. During this presentation, I demonstrate some of our current projects including the single optical fiber probe developed for optogenetics, implementation of high precision microprojection and imaging device for optical programming of large scale networks in the brain, combining optogenetics with other medical imaging modalities such as fMRI, and development of optoelectronic neuroprosthetic devices.