Description:

Title: "A serotonergic axon-cilium synapse"

Abstract:

Chemical synapses between axons and dendrites mediate neuronal intercellular communication. Using enhanced focused ion beam-scanning electron microscopy on samples with optimally preserved ultrastructure, we discovered synapses between axons and the primary cilia of target neurons. Mediated by serotonin released from axonal varicosities and the cilia-restricted serotonin receptor 5-hydroxytryptamine receptor 6 (gene: HTR6, protein: 5-HT6), activation of axo-ciliary synapses drives a RhoA-mediated signaling cascade that modifies nuclear actin to acetylate histones and increase chromatin accessibility. As a signaling apparatus with proximity to the nucleus, axo-ciliary synapses short circuit neurotransmission to alter the postsynaptic neuron’s epigenetic state.

Guest Speaker:

Shu-Hsien Sheu, MD, PhD; Team Leader, Chan Zuckerberg Institute. 

Description:

Title: “Sensing Coolness and Cold: Mechanism of TRPM8 Gating.”

Abstract: We have a long-standing interest in understanding how humans sense thermal and chemical stimuli through ion permeation via Transient Receptor Potential (TRP) ion channels. The TRPM8 (Transient Receptor Potential Melastatin 8) channel is the primary molecular transducer responsible for the sensation of coolness induced by menthol and cold temperatures in mammals. Additionally, our sensory adaptation to cold is mediated by the desensitization properties of TRPM8 channels. TRPM8 is also implicated in cold-evoked pain disorders and migraines, making its inhibitors a promising avenue for pain relief. Understanding the mechanisms of TRPM8 activation and desensitization by cold is not only a fundamental question but also has significant potential for therapeutic development. We have elucidated the structural and mechanistic bases of TRPM8 activation, desensitization, and inhibition. Our findings shed light on the molecular mechanisms underlying cold sensation and adaptation in mammals, as well as highlight the therapeutic potential of TRPM8 in treating neuroinflammatory diseases and cold-evoked pain. 

Brief summary of Dr Lee's research: Membrane transport proteins selectively recognize a variety of substrates of differing sizes and physicochemical properties for cellular transport, making them essential for the movement of key molecules and the transfer of information across cell membranes—events central to many important physiological processes. We utilize various structural and biophysical methods—including cryo-EM, electrophysiology, and radioligand flux and binding assays—to study three important transport processes: temperature- and irritant-dependent ion channel gating, drug and nutrient transport and inhibition, and polysaccharide transport for microbial cell wall synthesis. Studying these systems helps us understand the physiological and pathophysiological processes underlying somatosensation, pain, cancer, and bacterial or fungal infections.

Guest Speaker: Seok-Yong Lee, PhD; George Barth Geller Distinguished Professor of Molecular Biology; Professor, Departments of Biochemistry & Cell Biology; Member of the Duke Cancer Institute. 

Description:

*Friday October 4th 2024*

Talk info TBA

Guest Speaker: Carsen Strigner, PhD; Group Leader, HHMI Janelia Research Campus.

Stringer's lab develops algorithms for understanding large-scale neural activity. In addition, the lab works on general segmentation algorithms for cellular data, which enable fast and accurate processing of ~50,000 neuron recordings.

NOTE: This seminar is taking place on Friday so it does not conflict with SFN. 

Description:

Talk info TBA

Guest Speaker: Wade Van Horn, PhD; Associate Professor, School of Molecular Sciences Member, Biodesign Center for Personalized Diagnostics. 

Areas of Expertise: Biochemistry, Biophysics, Physical Chemistry. 

Description:

Talk info TBA

Guest Speaker: Sudha Chakrapani, PhD; Joseph T. Wearn, MD University Professor in Medicine; Director, Cryo-Electron Microscopy Core; Director, Cleveland Center for Membrane and Structural Biology; Case Western Reserve University.