Functional interactions between endoplasmic reticulum and mitochondria in Drosophila axons

Información del proyecto

ParaplegiaAxonsER

Identificador del acuerdo de subvención: 701397

DOI

10.3030/701397

Proyecto cerrado

Fecha de la firma de la CE 7 Marzo 2016

Fecha de inicio 1 Marzo 2017

Fecha de finalización 28 Febrero 2019

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 183 454,80

Aportación de la UE

€ 183 454,80

Coordinado por

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom

Objetivo

Axonal endoplasmic reticulum (ER) forms a continuous network of tubules that appears to occur ubiquitously in neurons, and has been compared to “a neuron within a neuron”. Its importance is suggested both by its apparent ubiquity, and by the identification of several causative genes for the axon degenerative disease, hereditary spastic paraplegia (HSP), that encode proteins that contribute to ER modeling. However, its physiological roles, and how it could influence axon degeneration, are poorly understood.

There is increasing awareness of the existence, nature and roles of contact sites between ER and other cellular organelles including mitochondria. Here I will explore these interactions and their functions in axons, in particular testing the model that ER architecture is important in regulating mitochondrial function in axons. My host laboratory has recently identified Drosophila mutants that lack one or more relevant HSP genes, and shown abnormalities in the level or continuity of ER in some genotypes.

I will use Drosophila HSP mutants to determine whether mitochondrial abnormalities arise with altered ER organisation. I will also test for colocalisation of a Drosophila Reep protein with ER-mitochondrial contact sites, and whether loss of this protein leads to abnormal mitochondria. Together these experiments will address whether ER-localised HSP proteins affect mitochondrial function.

Secondly I will examine whether mitochondrial Ca2+ handling is affected in these models. I will generate transgenic Drosophila that express mitochondrial and cytosolic Ca2+ sensors, and attempt to develop a suitable lumenal ER sensor. I will use these to test the levels and heterogeneity of Ca2+ concentrations in resting and active axons, and investigate how HSP mutants affect this.

My work will examine the interplay between ER and mitochondria in axons for the first time, and mechanisms of dysfunction that are relevant for human axon degeneration.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias biológicas › neurobiología
• ciencias médicas y de la salud › medicina básica › fisiología › fisiopatología
• ciencias naturales › ciencias químicas › química inorgánica › metales alcalinotérreos
• ciencias médicas y de la salud › medicina clínica › embriología
• ciencias médicas y de la salud › medicina básica › fisiología › homeostasis

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-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF)
  

Régimen de financiación

MSCA-IF-EF-ST - Standard EF

Convocatoria de propuestas

H2020-MSCA-IF-2015

Coordinador

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

• Aportación neta de la UEn: € 183 454,80
• Dirección: TRINITY LANE THE OLD SCHOOLS ; CB2 1TN CAMBRIDGE ; Reino Unido
• Región: East of England › East Anglia › Cambridgeshire CC
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 183 454,80