PhD Studentship: How Experience Shapes the Brain: Molecular Mechanisms of Brain Plasticity and Degeneration

How does experience shape the brain? We aim to understand why distinct experiences result in adaptation through learning, whilst others can lead to unsurmountable stress, psychiatric and behavioural disorders. We will test the hypothesis that experience results in structural modifications to cells that alter neural circuit connectivity patterns that in turn modify behaviour. The brain is made up of mostly water and molecules such as proteins, lipids and sugars that decay every day, so we eat and sleep to restore daily our cell biology. Synapses and changes in cell shape are made and unmade every day, as we go about our lives. And if cells change, connectivity patterns in the brain change: what are the consequences to behaviour, what we do, how we feel?

The brain is plastic: structural plasticity enable us to form new synapses and connectivity patterns as we learn and adapt to life challenges, encoding memory. Structural homeostasis constrains the brain’s ability to change, thus maintaining neural circuits stable. Exercise and learning increase structural plasticity, whilst homeostatic meachanism can lead to degeneration underlying neurodegenerative diseases (e.g. Alzheimer’s and Parkinson’s), neuro-inflammation and psychiatric disorders (e.g. depression). The cellular processes underlying structural brain change include neurogenesis and gliogenesis, cell loss, changes in cell shape, synapse formation and loss, modifying circuits a behaviour. As behaviour is a source of experience, we aim to find out how cycles of experience and behaviour modify our brain throughout life.

The aim of the project is to discover and test candidate molecular and cellular mechanisms underlying the switch between structural brain plasticity and degeneration in response to experience, and how this in turn modifies behaviour.

The resulting findings will help understand how the brain works, how we can maintain brain health and what causes brain disease.

Methods

We will use the fruit-fly Drosophila as a model organism, for its unparalleled, powerful genetics. With our findings and collaborative approach to discuss with psychologists, we will strive to link our findings to understanding human conditions. The approach will combine a wide range of techniques including: advanced genetics to manipulate genes and cells, molecular cell biology including CRISPR/Cas9 gene editing technology and transgenesis, microscopy, including laser scanning confocal microscopy and calcium imaging in time-lapse, computational imaging approaches for analysis of images and movie recordings, analysis of the connectome to identify neural circuits, stimulating neuronal function with opto- and thermo-genetics in vivo, recording and analysing fruit-fly behaviour, aided by computational data analyses tools.

Visit: https://more.bham.ac.uk/hidalgo/

Funding notes:

This is a PhD studentship with the Midlands Integrated Biosciences Training Partnership, funded by BBSRC and in partnership with the University of Warwick, Aston University, Harper Adams University, Coventry University, and the University of Leicester.

For more details please visit: https://warwick.ac.uk/fac/cross_fac/mibtp/ or https://www.birmingham.ac.uk/about/college-of-life-and-environmental-sciences/midlands-integrative-biosciences-training-partnership

How to apply:

To apply, please click the above 'Apply' button, make an account, and submit an application via the university online admissions portal. This link is unique to the MIBTP programme; please do not use any other link to apply to this project or your application may be rejected.

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