Modulating brain structural plasticity versus neurodegeneration via a novel mechanism involving neurotrophins and dopamine, Tolls and Kek truncated-Trk-like receptors in Drosophila.

Información del proyecto

TOLKEDA

Identificador del acuerdo de subvención: 794677

DOI

10.3030/794677

Proyecto finalizado el 20 Diciembre 2020

Fecha de la firma de la CE 28 Marzo 2018

Fecha de inicio 1 Septiembre 2018

Fecha de finalización 28 Diciembre 2020

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 195 454,80

Aportación de la UE

€ 195 454,80

Coordinado por

THE UNIVERSITY OF BIRMINGHAM
United Kingdom

Objetivo

The aim of TOLKEDA is to test the hypothesis that a novel molecular mechanism linking neurotrophins, Tolls and truncated Trk-like receptors modulates structural brain plasticity vs. neurodegeneration. The brain changes throughout life: structural plasticity drives generation of neurites, neurons and synapses to adapt and learn; their elimination maintains homeostasis, but causes neurodegeneration in ageing and disease. Brain disease is the major health burden in Europe, costing more than cancer and cardiovascular diseases put together, and its incidence will grow as the population ages. It is imperative to discover novel molecular pathways that can be targeted to treat brain disease. The Principal Investigator (PI) Dr Alicia Hidalgo recently discovered a novel Drosophila neurotrophin (DNT) mechanism formed of neurotrophins, Toll and truncated-Trk-like receptors, and demonstrated that it underlies neuronal number and synaptic structural plasticity in larvae. Preliminary evidence shows that the DNT system operates in the adult brain, overlapping with dopaminergic neurons (DANs). Dopamine is a key neuromodulator, and degeneration of DANs underlies neurological and neurodegenerative diseases, such as Parkinson’s disease (PD). The Experienced Researcher (ER), Jun Sun, is an expert in the dopaminergic system and Drosophila PD models. The timely collaboration between PI and ER will provoke synergy to address effectively the following research objectives (ROs): RO1: to create a map of DNTs, Toll-6, Kek-6 and DANs in the adult brain, using gene editing technology and neural circuit registration. RO2: to test whether altering the functions of DNTs, Toll-6 and Kek-6 causes structural brain deficits, including in the dopaminergic system, and whether they are linked to behavioural deficits and neuronal activity. RO3: to test whether manipulating the DNT/Toll-6/Kek-6 signalling module in the dopaminergic system can promote neuroprotection in a Drosophila PD model.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias biológicas › neurobiología
• ciencias médicas y de la salud › biotecnología médica › ingeniería genética › terapia génica
• ciencias médicas y de la salud › medicina clínica › cardiología › enfermedad cardiovascular
• ciencias médicas y de la salud › medicina básica › neurología › parkinson
• ciencias médicas y de la salud › medicina básica › fisiología › homeostasis

Palabras clave

• Drosophila
• structural brain plasticity
• neurodegeneration
• Parkinson's Disease
• neuronal survival
• cell death
• neurite
• Toll receptors
• truncated-Trk receptors
• neurotrophins
• dopamine

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2017 - Individual Fellowships
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2017

Coordinador

THE UNIVERSITY OF BIRMINGHAM

• Aportación neta de la UEn: € 195 454,80
• Dirección: Edgbaston ; B15 2TT Birmingham ; Reino Unido
• Región: West Midlands (England) › West Midlands › Birmingham
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 195 454,80