Job ID: 87292
PhD in Neuroscience
Position: Ph.D. Student
Deadline: 14 September 2022
Employment Start Date: 3 October 2022
Contract Length: 3 years
City: Nottingham
Country: United Kingdom
Institution: University of Nottingham
Department: School of Life Sciences
Description:
PhD Project Title: Mechanobiology of neurogenesis and synapse formation in the brain.
Project Overview:
Neurodevelopmental disorders, such as autism or schizophrenia, can be associated with an imbalance between inhibitory and excitatory neurotransmission in key brain regions. Dysfunctions in mechanisms that regulate neurogenesis and gliogenesis may, in part, be responsible for the increased susceptibility of individuals to developing such disorders. Neurogenesis is regulated by a multitude of biochemical and biophysical signals from extracellular sources. Our research group is interested in studying the mechanical cues and mechano-transduction signals that may be important in controlling neurogenesis in the maturing brain.
As the brain matures, new neurons are born and integrate into existing functional neural circuits. Maturing neurons form new synapses, many of which create new functional connections with neighbouring neurons. However, others are lost via synaptic pruning. The processes of synaptogenesis and synaptic pruning are regulated by extracellular signals, including the extracellular matrix, and by neighbouring glial cells. Our research group are also interested in the biophysical and mechanical signals that regulate synapse formation and synaptic pruning, particularly in the dentate gyrus of the hippocampus, a brain region involved in learning and memory formation.
Using interdisciplinary laboratory approaches, including novel in vitro brain slice culture models, fluorescence microscopy, calcium imaging, image analysis, and electrophysiology, the PhD student will investigate how extracellular cues, mechanosensitive ion channels and intracellular mechanotransduction signals regulate neurogenesis, synapse formation and glial cell-mediated synaptic pruning in the hippocampus.
This PhD project will provide the successful candidate the opportunity to advance our knowledge and understanding of the importance of mechanical cues and mechanosensitive ion channels in neurogenesis, synapse formation, and glial cell-mediated synaptic pruning.
The main end goal of this project is to identify novel molecular drug targets and pharmacological compounds that can regulate neurogenesis and synapse formation, with the overall aim of finding novel pharmacological tools to treat the symptoms of neurodevelopmental disorders.
The successful PhD candidate will work in a multidisciplinary collaborative laboratory and receive training in a range of research techniques including primary cell culture, immunofluorescence, proteomics, live-cell calcium imaging, and electrophysiology.
Enthusiastic and motivated candidates who are passionate about conducting cross-disciplinary research in neuropharmacology and bioengineering are encouraged to contact Dr Graham Sheridan in the first instance to discuss the project in more detail.
PhD eligibility criteria: only candidates who are eligible for UK home fee status can apply
PhD funding is for 3 years full-time and includes a monthly stipend and university registration fees
References:
– Hall et al. (2020) Mechanobiology of the brain in ageing and Alzheimer’s disease. Eur J Neurosci 53: 3851–3878. doi:10.1111/ejn.14766.
– Velasco-Estevez et al. (2020) Piezo1 regulates calcium oscillations and cytokine release from astrocytes. GLIA 68: 145–160. doi:10.1002/glia.23709.
– Velasco-Estevez et al. (2018) Infection augments expression of mechanosensing Piezo1 channels in amyloid plaque-reactive astrocytes. Front Aging Neurosci. 10:332. doi:10.3389/fnagi.2018.00332.
Please submit applications via email as a single PDF file to graham.sheridan@nottingham.ac.uk
– Letter of motivation
– Curriculum vitae and publication list
– Name and email address of two referees that support your application