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Exploring the role of the anti-ageing molecule sirtuin-1 in cellular senescence in primary human lung cells


National Heart and Lung Institute

Prof Peter Barnes FRS , Prof Louise Donnelly , Dr Jonathan Baker Friday, April 30, 2021 Funded PhD Project (UK Students Only)
London United Kingdom Biochemistry Cell Biology Data Analysis Immunology

About the Project

3-year BBSRC CASE studentship, in collaboration with AstraZeneca, commencing October 2021

The PhD student will be supervised by Professor Peter Barnes, Professor Louise Donnelly and Dr Jonathan Baker (Imperial College London) and Dr Werngard Czechtizky (BioPharmaceuticals R&D, Research and Early Development, Respiratory & Immunology).

We seek a highly motivated PhD student to study the mechanism of cellular senescence in the lung. Sirtuin-1 (SIRT-1), a key anti-ageing molecule, is reduced in several chronic diseases of accelerated ageing, including chronic obstructive pulmonary disease (COPD), cardiovascular diseases and type 2 diabetes. We have explored the molecular mechanisms leading to decreased SIRT-1 in COPD and shown involvement of oxidative stress-induced activation of PI3K-mTOR, increased microRNA-34a and p38 MAP kinase induced-activation of miR-570.

This PhD project will explore further the role of SIRT1 in cellular senescence using a variety of tool reagents. These include new inhibitors of mTOR and its downstream kinase p70S6K, activators of AMP kinase, novel antagomirs to block miR-34a and -570 and modified mRNA to restore SIRT-1 expression. We are also interested in their combinations to understand compensatory mechanisms.

We will study three cell models of cellular senescence, including replicative senescence, oxidative stress (H2O2), and DNA damage (doxorubicin, etoposide) in primary cells from human lung (small airway epithelial cells and fibroblasts) where we have characterized senescence pathways. The aim is to identify new therapeutic strategies and targets to treat and reverse cellular senescence in chronic lung disease.

This project is funded by the BBSRC and is part of an ongoing, productive, collaboration between researchers at Imperial College London and AstraZeneca. The successful candidate will be based at the National Heart and Lung Institute, Imperial College London, but will have the opportunity to also work in the research laboratories of the Early Respiratory and Immunology therapeutic area at AstraZeneca. This exciting collaboration creates a unique opportunity for scientific excellence and career development in translational research. 

Application Process

To apply, please submit a one-page personal statement detailing your academic background and research interests, a CV and contact information of two professional/academic references to NHLI PGR team via email () by Friday 30th April 2021. The studentship is expected to start in October 2021.

Eligibility

The ideal candidate should have an excellent academic track record and have obtained an undergraduate degree at 2:1 level or higher and, normally, a Master’s degree with merit or higher (or non-UK equivalents) in immunology, cell biology, biochemistry or another relevant field. Candidates without a Master’s level degree but with significant laboratory experience will be considered. Laboratory experience is essential and proficiency in flow cytometry, cell culture and data analysis are desirable. Eligible candidates should be self-motivated, proactive, have excellent oral/written communication abilities and be able to work well within a multidisciplinary translational research team.


Funding Notes

This position is available as a fully funded PhD studentship, including 3.5 years of tuition fees and provides a 3.5-year, tax-free stipend (Home candidates) at the standard Research Council London rate.

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