Investigating the metabolic and transcriptional regulation of lipid-associated macrophages

About the Project

Project Overview

Metabolic diseases such as obesity, liver steatohepatitis and atherosclerosis are increasingly prevalent worldwide and more emphasis is focused on identifying molecular targets for both prevention and treatment. Lipid-associated macrophages (LAMs) are specialized tissue macrophages responsible for processing and clearing lipid-derived products and debris and are central in the development and progression of metabolic disease. We have identified, in vivo, two subsets of LAMs, a homeostatic population with an efficient lipid handling and anti-oxidative properties and an inflammatory pathogenic LAM population which dysfunctional metabolism and apoptotic signature highly correlated with morbidities.

Given that LAMs are present in many lipid-rich tissues and associated with a plethora of metabolic and neurodegenerative diseases, investigating the mechanisms and pathways governing the 2 LAM subsets has a broad translational outreach and will provide us with future therapeutic tools to limit the expansion of the pathogenic population to limit disease-associated morbidities.

For this project, the applicant will be investigating the mechanisms and pathways inducing the transition from “good” LAMs to “pathogenic” LAMs. The applicant will use different in vitro models including primary and immortalized cell culture and targeting different pathways using Knockout models and CRISPR constructs, as well as available activators and inhibitors to determine the signalling pathways and identify transcription factors orchestrating the transition of LAMs. Outcome will include functional readouts such as bioenergetics, cholesterol efflux, apoptosis assays as well as gene and protein analysis.

Dib Group- Dr. Dib’s research interest aims to investigate the molecular mechanisms and metabolic control of lipid-associated macrophages (LAMs-also known as foam cells) in metabolic and non-metabolic disease.

School of Biological Sciences, University of Reading:

The University of Reading, located west of London, England, provides world-class research education programs. The University’s main Whiteknights Campus is set in 130 hectares of beautiful parkland, a 30-minute train ride to central London and 40 minutes from London Heathrow airport.

Our School of Biological Sciences conducts high-impact research, tackling current global challenges faced by society and the planet. Our research ranges from understanding and improving human health and combating disease, through to understanding evolutionary processes and uncovering new ways to protect the natural world. In 2020, we moved into a stunning new ~£60 million Health & Life Sciences building. This state-of-the-art facility is purpose-built for science research and teaching. It houses the Cole Museum of Zoology, a café and social spaces.

In the School of Biological Sciences, you will be joining a vibrant community of ~180 PhD students representing ~40 nationalities. Our students publish in high-impact journals, present at international conferences, and organise a range of exciting outreach and public engagement activities.

During your PhD at the University of Reading, you will expand your research knowledge and skills, receiving supervision in one-to-one and small group sessions. You will have access to cutting-edge technology and learn the latest research techniques. We also provide dedicated training in important transferable skills that will support your career aspirations. If English is not your first language, the University's excellent International Study and Language Institute will help you develop your academic English skills.

The University of Reading is a welcoming community for people of all faiths and cultures. We are committed to a healthy work-life balance and will work to ensure that you are supported personally and academically.

Eligibility:

Applicants should have a good degree (minimum of a UK Upper Second (2:1) undergraduate degree or equivalent) in Biomedical Sciences or a strongly related discipline. Applicants will also need to meet the University’s English Language requirements. We offer pre-sessional courses that can help with meeting these requirements. With a commitment to improving diversity in science and engineering, we encourage applications from underrepresented groups.

How to apply:

Submit an application for a PhD in Biomedical Sciences via our online application system.

Further information:

https://www.reading.ac.uk/biological-sciences/research

Enquiries:

Dr. Lea Dib, email: l.dib@reading.ac.uk

Funding Notes

We welcome applications from self-funded students worldwide for this project.

If you are applying to an international funding scheme, we encourage you to get in contact as we may be able to support you in your application.