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Brain structural plasticity, degeneration and regeneration: from molecules to behaviour


   School of Biosciences

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  Prof Alicia Hidalgo  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Brain structural plasticity, degeneration and regeneration: from molecules to behaviour

The aim of the project is to discover and test candidate molecular mechanisms underlying structural brain plasticity, degeneration and regeneration, and the link between molecules, structural cell change, circuits and behaviour. We will use the fruit-fly Drosophila as a model organism.

We aim to understand how the brain responds to environmental challenge, how it changes as we go through life, how experience shapes the brain, why does the brain degenerate as we age, how can we promote regeneration after injury.

The brain is plastic: it changes as we learn, enabling adaptation and memory, and then it degenerates as we age. The brain and spinal cord can also respond to stressors and injury. The human central nervous system (CNS) does not regenerate after injury or disease, but some animals can regenerate their CNS and this generally involves cell reprogramming, de novo neurogenesis followed by integration of new neurons into functional neural circuits. This means that cells can ‘know’ how to re-establish brain cell populations and circuits. In fact, the healthy brain is kept in balance between structural plasticity and homeostasis, resulting in normal behaviour. Structural plasticity enables change as we learn and adapt to environmental change, encoding memory. Structural homeostasis constrains the brain’s ability to change, thus maintaining neural circuits stable. Exercise and learning increase structural plasticity, sleep promotes homeostasis, whilst brain diseases are linked to loss of this balance, such as brain tumours (e.g. gliomas), neurodegenerative diseases (e.g. Alzheimer’s and Parkinson’s), neuro-inflammation and psychiatric disorders (e.g. depression). Conversely, the homeostatic mechanisms that keep the brain stable also slow down learning and prevent the brain from recovering in injury and disease.

The cellular processes underlying structural CNS change include neurogenesis and gliogenesis, cell death and cell loss, cellular reprogramming, changes in cell shape (generation or loss or axons, dendrites, glial projections), synapse formation and loss, altogether leading to neural circuit modification and modification of behaviour. We will investigate how experience, stressors and injury modify cellular processes and circuits and how this modifies behaviour. The molecular mechanisms underlying structural brain change are scarcely known. Discovering them will help answer how the brain works, how we can maintain brain health, promote regeneration after injury and treat brain disease. 

We will use the fruit-fly Drosophila as a model organism, for its powerful neurogenetics tools that allow from high resolution cell biology in vivo in the brain, to behavioural tests.

Aims:

to investigate, test and discover molecular and cellular mechanisms of structural brain plasticity, degeneration and/or regeneration and their consequences for behaviour, using the fruit-fly Drosophila as a model organism.

Methods 

We will use the fruit-fly Drosophila as a model organism, combining a wide range of techniques including:  genetics, 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 movies, stimulating neuronal function with opto- and thermos-genetics in vivo, and recording and analysing fruit-fly behaviour. 

Keywords: Drosophila, neuroscience, regeneration, repair, plasticity, behaviour

MIBTP FUNDED PROJECT

You can apply for funding under the MIBTP doctoral training programme of the BBSRC available via the School of Biosciences, University of Birmingham, for both UK and international applicants.

FIND OUT MORE HERE: https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/

Our project is within: "Understanding the rules of life" and "Integrated understanding of health".

APPLY HERE: 

https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/application/submission/

DEADLINE 20 JANUARY 2023

OTHER FUNDING OPPORTUNITIES

You can also apply with other sources of funding. For example, you could apply for a scholarship from your own country. 

PLEASE CONTACT ME at [Email Address Removed] if you are interested in doing your PhD with me, regardless of funding.


Funding Notes

MIBTP FUNDED PROJECT
You can apply for funding under the MIBTP doctoral training programme of the BBSRC available via the School of Biosciences, University of Birmingham, for both UK and international applicants. DEADLINE FOR MIBTP STUDENTSHIPS IS 20 JANUARY 2023
FIND OUT MORE HERE: https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/
Our project is within: "Understanding the rules of life" and "Integrated understanding of health".
APPLY HERE:
https://warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/application/submission/
OTHER FUNDING OPPORTUNITIES
You can also apply with other sources of funding. For example, you could apply for a scholarship from your own country.
PLEASE CONTACT ME at [Email Address Removed] if you are interested in doing your PhD with me, regardless of funding.

References

Visit our lab website: https://more.bham.ac.uk/hidalgo/
• Harrison N, Connolly E, Gascón Gubieda A, Yang Z, Altenhein B, Losada-Perez M, Moreira M, Hidalgo A (2021) Regenerative neurogenesis is induced from glia by Ia-2 driven neuron-glia communication. eLife10:e58756 DOI: 10.7554/eLife.58756
• Li G and Hidalgo A (2020) Adult neurogenesis in the Drosophila brain: the evidence and the void. International Journal of Molecular Sciences 21(18), 6653
• Guiyi Li and Alicia Hidalgo (2021) The Toll route to structural brain plasticity. Frontiers in Physiology. Frontiers in Physiology DOI: 10.3389/fphys.2021.679766
• Li G, Forero MG, Wentzell JS, Durmus I, Wolf R, Anthoney NC, Parker M, Jiang R, Hasenauer J, Strausfeld NJ, Heisenberg M, Hidalgo A (2020) A Toll-receptor map underlies structural brain plasticity eLife, 9: e52743 DOI: 10.7554/eLife.52743
o eLife Digest article 17 March 2020 dedicated to our paper: “How experience shapes the brain”
https://elifesciences.org/digests/52743/how-experience-shapes-the-brain
• Losada-Perez M, Harrison N, Hidalgo A. (2016) Molecular mechanism of central nervous system repair by the Drosophila NG2 homologue kon-tiki. Journal of Cell Biology 214, 587
• Kato, Forero and Hidalgo (2011) The glial regenerative response to CNS injury is enabled by Pros-Notch ad Pros-NFkB feed-back. PLoS Biology 9, e1001133

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