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Sympathetic and immune mechanisms underlying obesity

Objective

The era of molecular genetics has enabled the mechanistic dissection of brain circuits as well as the immune system in spectacular ways. However, the molecular and cellular organization of the sympathetic nervous system (SNS), which innervates all known organs, is essentially unexplored. In an attempt to push this frontier, we have recently uncovered a direct physical functional connection between the SNS and the adipose tissue. Further, we found this neuro-adipose junction to drive lipolysis and fat mass reduction (1). In this proposal we aim to define the molecular mechanisms that link SNS neurons, the immune system and the adipose tissue. A major entry point is our recent discovery of a novel population of Sympathetic Associated Macrophages (SAMs) that suppress the output of SNS. We propose to unravel their contribution to obesity in rodents (Aim 1) and in humans (Aim 2). Another major objective of this proposal is to establish a functional and molecular neuronanatomical map of the SNS, which defines subpopulations of neurons that specifically innervate fat (Aim 3). To achieve this, we will build molecular genetics tools for rapid non-invasive optocoustic visualization and functional probing of SNS circuits. A molecular and realistic atlas of the SNS will allow us to systematically access the functional anatomy of one of the most elusive tissues of the mammalian body and will form a blueprint upon which our neuroimmune mechanistic studies can be build. Our identification of the fundamental biological mechanisms that govern the neuro-adipose junction will set the stage for a new anti-obesity therapy that would circumvent the challenge of drug delivery to the brain, i.e. by targeting an excitatory drug directly to SAMs or sympathetic inputs in adipose tissue.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2017-COG

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Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 029 175,00
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 029 175,00

Beneficiaries (1)

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