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  The in situ molecular structure of active calcium ion channels


   Faculty of Biological Sciences

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Dr Rene Frank Prof Nikita Gamper  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

In the mammalian nervous system, specialized subcellular structures including synapses mediate learning and memory. The focal release of Ca2+ ions by ion channels is thought to be the signal that drives local, long-lasting structural remodeling within synapses. We are seeking a highly motived PhD candidate to investigate the structural mechanism of these fundamental cellular processes.

This interdisciplinary project involves exploiting recently developed mouse genetic reagents to determine the in situ 3D molecular structure of calcium ion channels and to investigate activity-dependent synaptic remodelling.The methods used will include: i) Electron tomography and computational image processing. ii) Cryogenic correlated light-electron microscopy (cryoCLEM) of synapses and thin vitreous sections. iii) Biochemical and genetic labelling of synaptic proteins. Applicants from all backgrounds in natural or physical sciences are encouraged to apply. Some experience with programming (e.g. Python, Matlab or similar) will be highly advantageous.

The University of Leeds has invested £10m in two 300 keV Titan Krios electron microscopes, a high-pressure freezer, and cryogenic light microscope. Thereby, the successful applicant will receive a training at the cutting edge of structural biology and molecular neuroscience.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2019:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference allowance
• Research Costs

Requirements:
At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.
EU candidates require 3 years of UK residency in order to receive full studentship

Not all projects advertised will be funded; the DTP will appoint a limited number of candidates via a competitive process.

https://biologicalsciences.leeds.ac.uk/directory/research-opportunities

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Project supervisors

Career overview

Dr René Frank received a PhD in Structural Biology of Multienzyme complexes from the Department of Biochemistry at the University of Cambridge in 2005. He completed a B.Sc. in Biochemistry at Imperial College, London, from 1997 to 2000. Dr Frank has held several postdoctoral positions, including a Postdoctoral Scientist role at the Department of Biochemistry, University of Cambridge from 2004 to 2006, and a Royal Commission for the Exhibition of 1851 Research Fellow at the Wellcome Trust Sanger Institute from 2006 to 2008. He then served as a Junior Research Fellow at Emmanuel College, Cambridge, and the Wellcome Trust Sanger Institute from 2008 to 2011, followed by a Postdoctoral Fellow position at the University of Edinburgh from 2011 to 2013. Most recently, he was a Postdoctoral Scientist at the MRC Laboratory of Molecular Biology in Cambridge from 2013 to 2018 before joining the Faculty of Biological Sciences at the University of Leeds as an Associate Professor and UKRI Future Leader Fellow. Dr Frank''s research focuses on the molecular architecture of synapses, particularly in relation to Alzheimer''s disease and neurodegeneration.


Research interests

Dr René Frank''s research focuses on the molecular architecture of synapses in the brain, particularly the postsynaptic membranes containing N-methyl D-aspartic acid receptors (NMDARs). Their work investigates how NMDARs mediate Ca2+-dependent signalling and interact with a variety of synaptic proteins to facilitate synaptogenesis and synaptic plasticity. Dr Frank employs mouse genetics alongside innovative biochemical methods, fluorescence imaging, and cryo-electron tomography to explore the postsynaptic membrane and its molecular mechanisms in vivo. Additionally, Dr Frank is interested in the role of synapses in Alzheimer''s disease (AD), specifically examining the signalling mechanisms that lead to the loss of glutamatergic synapses in AD and their connections to Aβ and tau pathologies. To address these inquiries, they utilise genetically engineered mice and in vivo protein labelling techniques.

View Dr René Frank's profile 
Career overview

Prof. Nikita Gamper obtained an MSc in 1995 and a PhD in Physiology from the Sechenov Institute of Evolutionary Physiology and Biochemistry in St Petersburg, Russia, in 1998. Following this, he served as a Postdoctoral Fellow at Tuebingen University in Germany from 1999 to 2001, and then at the University of Texas Health Science Center at San Antonio, USA, from 2001 to 2005. Since 2005, Prof. Gamper has held various academic positions at the University of Leeds, progressing from Lecturer to Associate Professor and then to Professor in Neuroscience. Additionally, he has been an Adjunct Professor of Pharmacology at Hebei Medical University in Shijiazhuang, China, since 2011, and has been a Wellcome Trust Investigator since 2019.


Research interests

Prof. Gamper''s research focuses on the regulation of cellular excitability, particularly concerning ion channels and G protein-coupled receptors. The primary emphasis of the group is on the regulation of excitability in peripheral pain-sensing (nociceptive) neurones related to pain signalling. They investigate the regulation of ion channels that influence the excitability and synaptic transmission of nociceptors, including GABAA, KCNQ (M-type) channels, Ca2+-activated Cl- channels, sensory TRP channels, and voltage-gated Ca2+ channels. Additionally, the group explores the modulation of various neuronal ion channels by G protein-coupled receptors (GPCRs) and the GPCR signalling networks within sensory neurones. Another research project focuses on the transcriptional regulation of neuronal ion channels in chronic pain states. Prof. Gamper employs a diverse array of advanced methods and techniques to address research questions at multiple levels, from individual molecules to whole organisms. These methods include biochemical and molecular biological approaches for studying proteins and genes, electrophysiology (patch-clamp and voltage clamp), and bioimaging techniques (such as live confocal and super-resolution microscopy) for examining individual cells, alongside various behavioural approaches to investigate neuronal signalling in vivo.

View Prof. Nikita Gamper's profile