Research interests
I am fascinated by the beautiful but complicated shape of individual neurons, and the complex intracellular logistics required to form, maintain and remodel these cells throughout life.
Neurons extend processes that cover vast territories, which allow them to directly connect with cells distant from the soma. Our research interest is to understand how neurons integrate the different extracellular cues that they receive at distinct parts of the cell in time and space to maintain and adapt their structure and connectivity. To this end, we study the interplay of short- and long-range trafficking and signalling, and how these events ultimately converge to initiate changes in neuronal morphology and physiology.
The formation and maintenance of neuronal connections requires morphological changes and is tightly coupled to activity-dependent events. In this regard, the neurotrophin BDNF provides an example of a highly regulated growth factor that triggers intracellular processes to initiate changes in cell shape. Moreover, its precursor, proBDNF, is also biologically active with largely opposing actions to those of mature BDNF, thus allowing for tightly controlled, bi-directional modulation of neuronal morphology by a single growth factor.
Our current research questions are:
What are the differential signals generated by pro- and mature neurotrophins?
We aim to broaden our understanding of the intracellular pathways activated by proneurotrophins by employing unbiased proteomic approaches, thus extending our work on mature BDNF and NT-3 signalling to include proBDNF. We are using the results of these screens as well as candidate approaches to dissect the molecular mechanisms of neurotrophin action on the cytoskeleton.
What decides if signals are processed locally or transmitted over long distances?
Morphological changes may be localised, to promote the growth or pruning of individual axonal and dendritic branches, or they can stimulate or suppress growth of the entire neuron. Using characterized nuclear responses to neurotrophin signalling as well as changes in morphology as read-outs, we are dissecting local processing of signalling cascades versus signal propagation along axons in compartmented devices.
In many neurodegenerative diseases, such as Alzheimer’s and Huntington’s disease, as well as motor neuron degeneration, impairment in axonal transport processes and dying back of neuronal connections precede cell death and are concurrent with onset of symptoms. In these and other instances of acute or progressive neuronal injury and degeneration, the balance between favourable and harmful signals is shifted. Understanding the signals and intracellular mechanisms that guide the remodelling of neuronal morphology in both supportive and adverse conditions may provide insights into these diseases and help direct therapeutic approaches.
PhD Supervision
Grace Hallinan. NeuroTraffic: Orientated neuronal networks for investigating mechanisms of tau propagation. Alzheimer’s Research UK/VC scheme. (2014-2017)
Prutha Patel. Are neurons that express mutant forms of tau fully competent to process BDNF-TrkB signalling? Gerald Kerkut Trust/BioSci. (2014-2018)
Aleksandra Pitera. Investigating axonal injury responses in tau-mediated neuronal degeneration. Alzheimer’s Society. (2016-2019)
Connor Maltby. Regulation of neuronal mRNA transport and protein synthesis by G-quadruplexes. (2016-2020)
Sarah Howard. Investigating the role of neuroinflammation on the accumulation and spread of tau pathology. MRC CASE.
Mercedes Beyna. Cellular and molecular mechanisms underlying ApoE4-mediated neuronal vulnerability. Biogen.
Dianne Lopez. Investigating tau propagation across neuronal networks. Gerald Kerkut Trust/BioSci.
Lauren McNicholas. Ups and downs of NMDA receptor phosphorylation by Fyn kinase: relevance for synaptic function in AD. Alzheimer’s Research UK.
Kirsten Williamson. Stress-induced transcriptional responses and their role in neurodegeneration. Alzheimer’s Society.
Lucy Scullard. Synaptic protein homeostasis in response to protein misfolding induced neurodegeneration. Kerkut Trust/BioSci.
Research group
Neuroscience
Affiliate research groups
Molecular and Cellular Biosciences, Southampton Neuroscience Group (SoNG), Institute for Life Sciences (IfLS)
Research project(s)
Investigating the mechanisms of membrane traffic and cell signalling
This project aims to delineate the cellular mechanisms that regulate cargo identification during endocytosis and autophagy and their impact on cell signalling and morphogenesis.
Dr Katrin DeinhardtSchool of Biological Sciences
Faculty of Environmental and Life Sciences
Life Sciences Building 85
University of Southampton
Highfield Campus
Southampton
SO17 1BJ
Room Number: 85/3040
Dr Katrin Deinhardt's
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