Molecular mechanism of CNS regeneration in Drosophila

Lead Research Organisation: University of Birmingham
Department Name: Sch of Biosciences

Abstract

The aim is to investigate the molecular mechanisms of central nervous system (CNS) regeneration, using the fruit-fly Drosophila as model organism. The CNS does not regenerate upon injury, leading to permanent disability, but damage and disease to the brain or spinal cord induce a limited regenerative response in glial cells, which if understood, could be harnessed to promote regeneration and repair. Glial cells of ensheathing cell lineages (which enwrap axons), divide, produce trophic factors that maintain neuronal survival, aid axonal re-growth and navigation, and re-enwrap axons, leading to limited recovery of behaviour. This response is evolutionarily conserved, from insects to humans, revealing an underlying a genetic mechanism. Understanding this mechanism is essential to control the proliferation and differentiation of stem and progenitor cells for therapeutic activation in vivo, and for cell transplantations.
Funded by BBSRC, the team of Dr Hidalgo discovered a gene network underlying the glial regenerative response. It involves the genes Notch and prospero (pros), and pros and NFkB, that together prime cells to respond to injury, enable a fast response and up-regulate the expression of kon-tiki (kon). And negative feedback that switches off kon, restores homeostasis and terminates the response to injury. Kon activates glial proliferation and differentiation onset, thus enabling glial regeneration; Pros inhibits proliferation, restoring homeostasis, and activates and maintains glial differentiation. In collaboration with mammalian experts, the Hidalgo team showed that this gene network is evolutionarily conserved in the mouse.
Still, how glial cells interact with neurons in response to injury is not understood.
Here we will ask: 1) why do neurons improve when glial cells regenerate? Is this driven by a neuronal ligand or receptor for glial kon? 2) Is NFkB activated in glia by Toll receptors?

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1790826 Studentship BB/M01116X/1 03/10/2016 25/03/2021 Elizabeth Catherine Connolly
 
Title Novel method to investigate regeneration and repair in adult Drosophila flies 
Description We are setting up a protocol to investigate regeneration and repair in adult Drosophila fruit-flies. We carry out contusion injury in the fly ventral nerve cord, and monitor survival, recovery and cellular responses to injury. Lizzie Connolly is supervising an MIBTP rotation student who is currently carrying on work to set this method up in our lab, and with which Lizzie will carry on working. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Year Produced 2020 
Provided To Others? No  
Impact We are currently setting up and testing the method. It has not optimised yet, and it has not been used in any research publication yet. 
 
Description "From tiny fruit-flies to great discoveries" at Green Heart Celebrations 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Celebrations for the Green Heart at the University of Birmingham, June 2019
Year(s) Of Engagement Activity 2019
 
Description Brain Awareness Week 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact A week of activities all about neuroscience research takes place each year with talks being held in institutions, cafes and pubs. The main event I participated in, and will participate in again next year, is the event held at the ThinkTank in Birmingham for the general public and mainly children. We show people the flies, how we use them and explain why we use them. We also have badge making activities and children can make their own fly brain to take home with them.
Year(s) Of Engagement Activity 2017
 
Description Brain Awareness Week 2019 at the ThinkTank Museum, March 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact "From tiny fruit-flies to great discoveries" celebration of international Brain Awareness Week. Outcome to increase public awareness of brain research
Year(s) Of Engagement Activity 2019
 
Description Debate from panel of scientists after showing a film, for Brain Awareness Week 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Panel discussion on concussion for Brain Awareness Week. Raising public awareness of brain research, and here focusing on stem cell research, brain damage, regeneration and repair.
Year(s) Of Engagement Activity 2020
 
Description Hands-on science at Museum Lates, ThinkTank Science Museum and University of Birmingham, October 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact "From tiny fruit-flies to great discoveries" Hands-on science at Museum Lates, ThinkTank Science Museum and University of Birmingham, October 2019
Year(s) Of Engagement Activity 2019
 
Description Open Days 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Students from around the country attend Open Days every year and several members of the lab, myself included, showcase our research. We explain how and why we use fruit flies, what are research is all about and discuss why the University is such a good place to study. As I had completed my undergraduate course at Birmingham, I also had extra insight into how well the undergraduate course was run and could answer most questions prospective students had.
Year(s) Of Engagement Activity 2016,2017,2018
 
Description School Visit 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 2 members of the lab, myself included, visited a primary school to teach Year 3 students about using fruit flies in research. We discussed why we use use them, how we use them and the impact they have had, and continue to have, on the world of research. We also attended a science festival after school where we engaged with parents, carers and teachers, enabling us to go a little further into detail about the work we do.
Year(s) Of Engagement Activity 2018