Project description
Adrenal organoids genetically engineered
The adrenal glands are a pair of small walnut-sized organs sitting on top of your kidneys. They produce hormones essential for regulating metabolism, the immune system, blood pressure and your response to stress among others. Adrenal gland malfunction (adrenal insufficiency) can be life-threatening. The GHSO project is developing a novel adrenal-like organoid, a 3D self-assembled cellular structure derived from human embryonic stem cells with capacity to produce adrenal hormones. Once this ground-breaking task is accomplished, GHSO will create adrenal organoids genetically engineered with common mutations to exhibit adrenal insufficiency. In parallel, the in vitro organoids will be implanted in vivo to assess its capacity to reverse the disease, accelerating the development of more effective treatments for adrenal insufficiency.
Objective
The adrenal cortex is essential for life; it is the primary site of steroid synthesis, producing glucocorticoids, which affect carbohydrate metabolism and mediate the mammalian stress response and mineralocorticoids, which control blood volume and salt homeostasis. Adrenal insufficiency (AI), which can be life threatening, is cause by a number of adrenal disorders, and lifelong management of these patients with exogenous steroids can be challenging. No drug suitably mimics the diurnal pattern of cortisol noted in healthy individuals, and objective variables to measure hormonal replacement therapy quality are lacking. The ability to generate steroid-producing cells from pluripotent stem cells through cell reprogramming, a process where a specialized cell type is induced to transform into a different cell, offers a new paradigm for functional studies, modelling human disease and drug testing and eventually can be used as a cell source for cellular therapies for patients suffering from adrenal conditions. This proposal aims to develop methodologies to generate adrenal-like organoids from human embryonic stem cells (hESCs), which have not been generated so far, without requiring overexpression of exogenous transcription factors and test them in in vivo models of adrenal insufficiency. Because small molecules provide several distinct advantages in controlling protein functions (e.g. temporally controllable, reversible, tunable and tractable) I will utilize them for a faster, more efficient, and directed cellular reprogramming. CRISPR-Cas9 genome engineered steroid-producing organoids harbouring common mutations found in congenital adrenal hyperplasia (CAH), the most common type of AI, will be generated and used as a disease modelling platform to study CAH. This proposal aims to accelerate the translation of this promising bench research to patients affected by adrenal insufficiency over the next 10 years.
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 medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences biochemistry biomolecules carbohydrates
- natural sciences biological sciences genetics genomes
- medical and health sciences basic medicine physiology homeostasis
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
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.
MSCA-IF-GF - Global Fellowships
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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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.
01069 DRESDEN
Germany
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.