Understanding the Role of Vitamin B6 Homeostasis in Health and Disease

Project Overview

Research Background

The active form of vitamin B6, namely pyridoxal 5’-phosphate (PLP), is a versatile enzyme catalyst with a double-edged sword. On one hand PLP is an essential cofactor for >4% of all enzymes. On the other, PLP imbalance in the cell is the cause of several inherited epilepsy disorders, and is associated with increased risk in cancer, cardiovascular and other common diseases. The cellular level of PLP therefore needs to be tightly controlled. How this homeostasis is achieved is an important, yet poorly investigated question.

Project objectives

We hypothesize that the biosynthesis, processing and delivery of PLP is mediated via an intricate interplay of diverse cellular proteins. This DPhil project will combine biochemical, structural and proteomic approaches in order to construct an integrated picture of B6 metabolism and homeostasis in the human cell.

The experimental objectives are to:

  1. determine how PLP is delivered to the various cellular enzymes that require it, using structural, biophysical and biochemical assays;
  2. reveal protein-protein interactions crucial for the PLP biosynthesis and delivery, using proteomics and cell-based approaches;
  3. identify novel therapeutic targets for B6-associated disorders where current treatment is not effective, to enable drug discovery.

Training Opportunities

Through this project the student will:

Theme

Protein Science & Structural Biology and Endocrinology & Metabolic Medicine

Admissions

Project reference number: 1002

Funding and admissions information

Supervisors

Name Department Institution Country Email
Associate Professor Wyatt W Yue Structural Genomics Consortium Oxford University, Old Road Campus Research Building GBR wyatt.yue@sgc.ox.ac.uk
Dr Kilian Huber Structural Genomics Consortium Oxford University, NDM Research Building GBR kilian.huber@sgc.ox.ac.uk

There are no publications listed for this DPhil project.