Vascular and hormonal interactions in the adrenal cortex
Adrenal cortex structure and function evolve with age and this phenomenon could be the consequence of vascular dysfunction. In particular, ageing is associated with increased nodulation of the adrenal cortex in the general population, which could represent a compensatory overgrowth following ischemic changes due to atherosclerosis or hypertension. The aim of this project is to investigate organ-specific vascularisation in the adrenal cortex and its interaction with adrenal cortex zonation, aldosterone production and formation of aldosterone producing adenoma.
The project will explore the interconnection of the vascular and steroidogenic components of the adrenal cortex during development and after physiological and pathological challenges. This will be performed in different genetically modified mouse models, including mice expressing Cre recombinase specifically in the zona glomerulosa of the adrenal cortex crossed with mT/mG mice, allowing observation of adrenal cortex morphology and the typical adrenal cortex lineage conversion. Those mice will also be crossed with retinoic receptor α knock-out mice, in which we have shown age- and sex-dependent disorganisation of the adrenal cortex, which are associated with vascular abnormalities and reduced expression of VEGF-A. Analyses will be performed at different ages and in both sexes. Analyses will include innovative imaging of the adrenal cortex, including the use of a newly developed multi-photon fibre-scope in living animals and lightsheet microscope imaging. Methods will also be developed to measure vascular reactivity in freshly isolated adrenal arteries and measure oxidative stress on frozen adrenals as well as vascular remodelling on isolated arteries. Secondments are planned with the Universidad Autónoma de Madrid and Intelligent Imaging (3I).
- Qualifications: Masters Degree (MSc, MS, MRes) in one of the following areas: biomedical science, biotechnology, biochemistry, molecular biology.
- Experience: Experience in experimental laboratory work is essential. Practical experience of animal handling, knowledge and/or experience of the regulations covering animal experimentation, experience of molecular science laboratory procedures are desirable.
- Knowledge & skills:Knowledge on pathophysiological mechanisms of disease, skills in animal manipulations and/or molecular biology are desirable.
- Attitude and disposition: Good interpersonal skills to allow working as part of a team, strong work ethics, self motivation, initiative and independent thought/working, problem solving skills including a flexible and pragmatic approach.
- Other circumstances: Although knowledge of French is not a prerequisite, the applicant will be offered French classes in order to interact with the local PhD programme.
Secondments: At Intelligent Imaging (3I), ESR10 will learn how to image and analyse adrenal vasculature in 3D (1 months), followed by sequential 1-2 week placement with 3I once samples have been prepared and for the purpose of imaging those samples and developing the imaging and analysis protocol. 2. In the Briones lab at UAM, ESR10 will be trained on the analysis of mechanisms underlying vascular dysfunction (2 months).