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Staff Profile

Dr Sabrina Mackinnon

Research Associate

Background

I am a Research Associate in Wyatt Yue’s lab where we aim to advance the understanding and treatment of rare metabolic disorders through the discovery of novel binding sites on disease-related enzymes, looking at how such enzymes interact with themselves and with other proteins, and by studying enzymes in a more native environment to explore their non-canonical – ‘moonlighting’ – functions.

Within the university, I am a member of the following:


My research to date has focussed on using fragment screening by X-ray crystallography, paired with enzyme activity and binding assays, to identify and improve small molecule inhibitors for the treatment of inborn errors of metabolism for which the pathogenic driver is accumulation of a toxic substrate.

Qualifications

D. Phil in Clinical Medicine                                                                                                2015 - 2020

Nuffield Department of Medicine, University of Oxford

  • Thesis title: Development of small molecule therapies for inborn errors of metabolism.
  • Supervised by Associate Professor Wyatt Yue and Professor Paul Brennan
  • Brief synopsis: Fragment screening by X-ray crystallography to identify, optimise and characterise small molecule inhibitors of metabolic enzymes for the treatment of metabolic disorders.
  • Funded by the Nuffield Department of Medicine Prize Studentship.
  • Maintained research blog: https://openlabnotebooks.org/category/scientist/sabrina-mackinnon/
  • Awards: ‘Best scored’ poster at Study of Inborn Errors of Metabolism (SSIEM) annual conference (2016). Travel scholarship (€760 plus registration fee) for oral presentation at SSIEM annual conference (2018).

Pass with minor corrections 16th April 2020. Received Leave to Supplicate 3rd August 2020.


BSc (Hons) Bioscience with Biomedical Sciences                                                         2011 - 2014 

Robert Gordon University, Aberdeen.

  • Dissertation: Influence of Cytochrome P450s in metabolic disease.
  • Final year research project: A 16S rDNA fingerprinting assay for identification of unknown microorganisms.
  • Nominated for Top Biology Student in Scotland Society of Biology award.

First Class Honours degree with Society of Biology 'Top Biology Student in University' prize.


Previous Positions

Postdoctoral Research Scientist - Metabolic Enzymes and Disorders                     2019 - 2021

Centre for Medicines Discovery, University of Oxford. Collaboration with Evotec, funded by Lab282 grant.

  • Large-scale expression, purification, and crystallisation of target protein
  • Determination of X-ray crystal structures with inhibitor compounds
  • Development of activity and solution binding assays for target protein
  • Characterisation of inhibitor kinetics and binding
  • Regular communication of results and plans to industrial collaborators.

    Research

    Current Work

    During my PhD, I worked on optimising approaches to protein production, crystallisation, biochemical and biophysical assays, fragment screening by X-ray crystallography and structure-guided drug design and applying them to develop inhibitors for two drug candidate targets. As a Research Associate here at Newcastle University, I am currently working on improving the potency of the molecules that I had developed in my PhD, to advance them towards clinical candidates. In a broader sense, my research interests lie in developing methodology for early drug discovery in rare metabolic disorders with the aim of developing first-in-class drug candidates and de-risking new drug discovery targets.

    Expertise

    Specialist knowledge in metabolic enzymes and disorders

    X-ray crystallography for hit finding and hit validation

    Luminescence and fluorescence-based assays to characterise potency, selectivity and mechanism of enzyme inhibitors

    Structure-guided compound design and in silico docking of designed compounds

    Structure-guided prediction of mutation effects


    Publications