EASTBIO Exploring physiological impacts for bioactive lipids on mucosal immune functions during aging

Aging is a series of processes with time-dependent deteriorative functional changes of organs, leading to a progressive disability of the organism in response to both internal and environmental stresses. Senescence-associated changes of immune responses in the respiratory tract play important roles in dysfunction of ‘normal’ aging epithelium (e.g. lung, gut) and the genesis of chronic lung/bowel diseases such as chronic obstructive pulmonary disease, IBD and bowel cancer. With increased life expectancy, a thoroughly advanced understanding how the epithelium undergoes physiological and immunological changes with age is needed for the success of public health programmes.

Bioactive lipid mediators play critical roles in maintaining body homeostasis and have divergent effects in response to internal (e.g. age-relate genetic alterations) and external (e.g. life style, smoking, exposure to pollution, etc) influences. Prostaglandins (PGs), especially PGE2, are important lipid mediators which are produced in homeostatic tissues at physiological levels. PGE2 exerts its biological actions through binding to its receptors termed EP1-EP4. While engagement of EP2 and EP4 results in activation of cAMP signalling, EP1 and EP3 couple to activate calcium signalling and down-regulate cAMP signalling, respectively. PGE2 regulates many physiological processes, e.g. it mediates the pain response, fever generation (via EP3) and stress behaviour, fertilization facilitation, bone formation and other important processes. We and others have recently defined that PGE2 has profound impact on regulating both tissue resident and systemic immune responses. For example, PGE2 regulates effector T cell responses to environmental antigen stimulation and gut innate immune homeostasis (refs 1,2). During the process of aging, levels of PGE2 are altered in most tissues including the lung and gut, which is inversely correlated with the progressing dysfunction of tissue homeostasis and dysfunction of organs.

In this PhD project we propose to study how bioactive lipid mediators are changed and how these changes modulate epithelial immune responses by focusing on adaptive and innate lymphocytes during physiological aging. We will employ cutting-edge immunological, physiological and genetic approaches to investigate the link between the lipid pathways and aging-associated lung immune dysfunction. We will also integrate the analysis of genome-wide gene expression data (e.g. microarray or RNA-sequence) and lipidomic data (e.g. arachidonic acid metabolites) to address the links among lipid mediators, transcriptomic networks and lung immune phenotypic traits in the normal aging process. Success in this project will help us to improve the understanding of the biology for immunological senescence, to ameliorate the negative consequences of advanced age, and to promote human health.

In terms of training, student involved in this project will gain a wide range of knowledge and skills in molecular biology, cellular biology and immunology, lung physiology and systemic biology. Student will also learn skills for statistical analysis of genomic and lipidomic data. Furthermore, students will receive excellent training on in vivo skills for working with rodent animals and on other skills for researcher development. The student will be assessed and benefit from the expertise in the well-established postgraduate committee embedded within the MRC Centre for Inflammation Research.


Application Process:

For instructions on how to apply for an EASTBIO PhD studentship please refer to http://www.eastscotbiodtp.ac.uk/how-apply-0

Contact Dr Chengcan Yao [Email Address Removed] before you apply.

We anticipate that our first set of interviews will be in the week commencing 10th February 2020 with awards made the following week.

Please submit all required documents directly to [Email Address Removed]

The research group is located in the University of Edinburgh Centre for Inflammation Research; a world-class research environment at the interface between biological and medical science, with multidisciplinary groupings focused on inflammation, infection, disease and repair. The Centre is based within the Edinburgh Medical School in the outstanding facilities of the Queen’s Medical Research Institute at the site of the Royal Infirmary of Edinburgh hospital, maximising future translational opportunities.