Investigating the metabolic response of low and high dietary vitamin A intake in humans using cell and mammal models

Description

Introduction: Nutrients we consume from food have many important biological roles in relation to growth, development and ageing in humans. Vitamin A is an essential nutrient for humans and is only available through diet or supplementation. In food it has two principal forms and sources (1) as retinol or retinyl esters present in animal products and fortified foods or (2) as pro-vitamin carotenoids present in vegetables and fruit which are in-vivo converted to retinal and retinol. Vitamin A is fat soluble and is stored primarily in the liver in humans. Vitamin A deficiency remains a serious health problem in developing countries and is most common in children and pregnant women; globally, vitamin A deficiency is estimated to impact approximately 30% of children under the age of five years leading to blindness and immune-related deaths. Food fortification and oral high-dose supplementation are being applied to reduce prevalence of deficiency, but recent data is suggesting that uncoordinated supplementation and fortification of foods can lead to acute and chronic vitamin A toxicity through long-term accumulation in the body which effects the liver, nervous system and musculoskeletal system. Understanding the metabolic consequences of vitamin A deficiency and excess (toxicity) in humans is important to be able to define appropriate intake guidelines, and in particular to refine the current upper intake levels of this nutrient which is currently debated globally.

Proposed PhD research: In the proposed PhD research you will further investigate the associations of metabolic perturbations related to vitamin A deficiency and excess in mammals. Specifically, you will (1) Use cell line, tissue explant culture studies and already available human cadaver samples to investigate metabolic changes in deficiency and toxicity and determine whether cell, tissue and animal models represent metabolic changes observed from existing model data; (2) use cell line, tissue explant and animal models to associate metabolic changes with cellular and tissue morphology and function (e.g. liver hypertrophy) and define vitamin A levels associated with deficiency and toxicity and (3) to determine if provitamin A sources can contribute to the risk of vitamin A excess and if current guidelines will need to include these forms for upper level determinations. You will receive training in biochemistry techniques, cell and tissue culturing, untargeted and targeted metabolite analysis and computational analysis of omics datasets. You will integrate into research groups at the Universities of Liverpool and Newcastle composed of PhD students, post-doctoral researchers and technical staff.

Applying: Applications should be made to project supervisors in the first instance via CV and cover letter. This is for all applications. Only when a candidate has been selected following interview will a formal online application be required.

Supervisors: 

Prof Warwick Dunn
Warwick.dunn@liverpool.ac.uk

Prof Georg Lietz
Georg.lietz@newcastle.ac.uk