Staff Profile

Biography

Wyatt Yue is a structural biologist with an MA (Biochemistry) from University of Oxford, and a PhD (Crystallography) from Birkbeck College London. Wyatt takes up the Chair of Structural Biology at Newcastle University Biosciences Institute, after leading the Metabolic & Rare Disease team at Centre for Medicines Discovery University of Oxford for over a decade. In 2021 he was awarded the inaugural Harrington UK Rare Disease Scholar. His research over the years has been supported by funding from UKRI (MRC, BBSRC, Innovate UK), charity (e.g. Wellcome, LifeArc, Action Medical Research), and the biotech/pharma industry (e.g. Pfizer, Bicycle Therapeutics, Atavistik Bio). Wyatt sits on the Management Team for the Newcastle Centre for Rare Diseases, and holds a visiting professorship at University of Oxford. He led the successful BBSRC-Alert bid in 2024 to build cryo-EM infrastructure in North East England.

Currently he leads a work package in the Horizon Europe funded consortium "Reconstruction and Computational Modelling for Inherited Metabolic Diseases" (Recon4IMD).

Recently he becomes a co-lead of NE BRIDGE, a collaborative initiative that brings together academia, the NHS and industry to strengthen rare disease therapeutic translation across the North East.

Group page

www.staff.ncl.ac.uk/yuelab/

Personal page

wyattyue.github.io

Structural Biology of Metabolic Enzymes

Wyatt specialises in the use of structural, biochemical and chemical biology approaches to study diverse metabolic protein families in the human genome. His team has to date determined structures by x-ray crystallography and cryo-electron microscopy, of >70 different human metabolic enzymes and complexes (>240 structures in total). Wyatt’s team adopts novel approaches in recombinant co-expression and endogenous isolation of multi-enzyme complexes, to delineate protein-protein interactions. Recent work includes frataxin-FeS cluster assembly complex, glycogenin-glycogen synthase complex, and TRiC chaperonin.

Drug Discovery for Rare Metabolic Disorders

The team’s vision is to translate basic science into design of small molecule therapeutics for rare diseases with unmet need. Disease-associated metabolic enzymes often lead to aberrant flux and accumulation of toxic metabolites. Therefore, pathway manipulation to reduce flux to the defective enzyme, through substrate reduction approach, could have therapeutic benefit. To this end, Wyatt’s team has carried out structure-based small molecule discovery for novel targets GALK1, HAO1, GYS1 and AASS to kick-start hit-to-lead and lead optimisation programmes, towards development of new therapies for rare metabolic disorders.

Module co-Leader & Lecturer, BGM3064 - Stage 3 lectures, seminars and workshops in Applied Biochemistry

Lecturer & Practical leader, BGM2060 - Stage 2 lectures and practical in Proteins and Enzymes

Lecturer, BGM2062 - Stage 2 lectures in Advanced Protein Analysis

Lecturer, MMB8018 - MRes seminar 

• Articles

  • Blomgren LKM, Huber M, Mackinnon SR, Burer C, Basle A, Yue WW, Froese DS, McCorvie TJ. Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase. Nature Communications 2024, 15, 3248.
  • McCorvie TJ, Adamoski D, Machado RAC, Tang J, Bailey HJ, Ferreira DSM, Strain-Damerell C, Basle A, Ambrosio ALB, Dias SMG, Yue WW. Architecture and regulation of filamentous human cystathionine beta-synthase. Nature Communications 2024, 15, 2931.
  • Mackinnon SR, Krojer T, Foster WR, Diaz-Saez L, Tang M, Huber KVM, von Delft F, Lai K, Brennan PE, Arruda Bezerra G, Yue WW. Fragment Screening Reveals Starting Points for Rational Design of Galactokinase 1 Inhibitors to Treat Classic Galactosemia. ACS Chemical Biology 2021, 16(4), 586-595.