Developments in neuroscience
The first webinar of 2021 is part of our dedicated Early Career Researcher (ECR) series. This online event will be chaired by Professor Clare Stanford, Emeritus Professor of Translational Neuropharmacology at UCL and Associate Editor of our Neuronal Signaling journal. During this session, we will hear from four ECRs who will share their current work in neuroscience:
- Louis Dwomoh (University of Glasgow) will discuss the disease modifying effects of targeting the M1 mAChR with a novel positive allosteric modulator in prion disease mice. He will show that deficits in learning and memory in prion neurodegeneration is restored by acute intra-peritoneal administration of VU0486846. In addition, chronic administration of these prion neurodegeneration mice with VU0486846 increased survival compared to prion mice treated with a vehicle. Using mass spectrometry-based proteomics, he will show that proteins that are elevated in prion neurodegeneration are associated with neuroinflammation, neurodegeneration and other key disorders in the CNS.
- Shaun Sanders (University of Guelph) will talk about the palmitoyl acyltransferase ZDHHC14 controls Kv1-family potassium channel clustering at the axon initial segment. One key factor that controls the threshold of neuronal excitability is the clustering of voltage-gated ion channels at the axon initial segment (AIS), the proximal part of the axon that regulates whether or not a neuron fires a nerve impulse to its neighbours. Modification with the lipid palmitate, through a process called palmitoylation, controls targeting of neurotransmitter receptors and associated ‘scaffold’ proteins to neuronal synapses and several palmitoyl acyltransferases (PATs) are implicated in this process. Shaun has identified a PAT enzyme called ZDHHC14 as a direct interactor and regulator of scaffold proteins and potassium channels at the AIS. This is the first identification of a role for ZDHHC14 in neurons and the first description of palmitoylation-dependent control of AIS ion channel regulation.
- Michelle Sahai (University of Roehampton) will present her work on elucidating the molecular mechanism of action of stimulant new psychoactive substances (NPS) that target the high-affinity transporter for dopamine. This talk will describe how computer simulations are used to investigate in 3D structural models of DAT, embedded in physiologically-relevant environments, what determines binding specificity and the mechanisms triggered by NPS in DAT, in comparison and in relation to the binding of its substrate, dopamine (DA). The effects of these drugs are complex and understanding the molecular mechanism depends on detailed information about the binding modes and the dynamic consequences of the ligand-DAT interactions.
- Janosch Heller (Dublin City University) will talk about how using super-resolution single molecule localisation microscopy (SMLM) can help revealing the nano-environment of tripartite synapses – the intricate relationship of astrocytic processes and synapses across the brain. This imaging technique relies on the sequential activation, imaging and bleaching of a sparse subset of fluorescent molecules. Thus, images can be obtained with sub-diffraction resolution by localising individual activated molecules in each frame. Using dSTORM, Janosch was able to localise cytoskeletal proteins as well as clusters of receptors and transporters in astrocytic and neuronal membranes in fixed cultured cells and in brain slices.
Register now for this free webinar!