Project description
Understanding type 2 diabetes pathophysiology for disease-modifying strategies
Type 2 diabetes (T2D) affects 1 in 10 adults worldwide and leads to 1.5 million deaths annually. Abnormal transcriptional programmes in pancreatic β-cells contribute to T2D, but our understanding of this remains incomplete. Current drug therapies primarily address hyperglycemia rather than the underlying causes of the disease. The MSCA-funded HuPIPA project aims to elucidate variations in β-cell transcriptional states. It will identify key cellular states by investigating regulatory responses to perturbations, offering insights into T2D pathophysiology and contributing to the development of disease-modifying strategies. The project will expand upon the Human Cell Atlas concept to establish the Human Pancreatic Islet Perturbation Atlas, characterising cell state dynamics through various perturbations.
Objective
Type 2 diabetes (or T2D) is a heterogeneous disease that affects nearly 1 in 10 adults worldwide, directly causing 1.5 million deaths each year. Human genetics and single cell genomic studies show that abnormal pancreatic β-cell transcriptional programs play a crucial role in type 2 diabetes. However, we lack an understanding of how this is translated into impaired β-cell function or mass.
Consequently, existing drug therapies for T2D aim to alleviate hyperglycaemia, but do not target causal mechanisms.
My overarching goal is to understand variation of β-cell transcriptional states.
I postulate that even if an infinite number of perturbations are conceivable, only a finite number of cell states exist. Identifying and characterizing major cellular states, by studying regulatory responses to perturbations could provide insights into T2D pathophysiology, and pave the way for disease-modifying strategies.
The concept of Human Cell Atlas currently depicts the cells landscape under one theoretical average condition, and does not represent the broad range of possible cell states that exist in different conditions. I'll be extending this concept towards the production of a Human Pancreatic Islet Perturbation Atlas (HuPIPA), which has the potential to be the first atlas characterizing cell states dynamics through multiple perturbations. I will harness this resource to unravel T2D mechanisms and to discover candidate therapeutic strategies.
To this end, I will design a large-scale single-cell multiomics experiment of human islets facing chemogenetic perturbations. I will
develop a novel statistical tool for the analysis of single-cell multiomics data under a broad range of conditions, and perform an
integrative analysis with T2D human genetic and single cell datasets.
This project, at the junction of statistics, genetics and computer science, has the potential to provide new knowledge for a better
understanding and treatment of T2D.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine physiology pathophysiology
- medical and health sciences clinical medicine endocrinology diabetes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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08003 Barcelona
Spain
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