Matthew Brook

Principal Investigator (UoE/CVS) and Lecturer (UoE/ZJE)

  • Centre for Cardiovascular Science

Contact details

Address

Street

Centre for Cardiovascular Science
Queen's Medical Research Institute
University of Edinburgh
Edinburgh Bioquarter
47 Little France Crescent
Edinburgh

City
Post code
EH16 4TJ

Biography

Qualifications

BSc Biochemistry: University of Essex

MPhil Biochemistry: University of Manchester (Regulation of proliferation and differentiation of the rat intestinal epithelium)

PhD Molecular Biochemistry: Imperial College London (Regulation of TNF-alpha gene expression by p38 mitogen-activated protein kinase)

Responsibilities & affiliations

Biochemical Society - Member of Research Area I (Genes) panel & Local Ambassador for University of Edinburgh

Centre for Cardiovascular Sciences - Research Integrity Academic Lead

Undergraduate teaching

Assistant Professor at Zhejiang University-University of Edinburgh (ZJE) Institute, lecturing on the Biomedical Sciences Joint Honours degree program.

Joint Coordinator of Years 3&4 for the Integrated Biomedical Sciences (BMS) and Biomedical Bioinformatics (BMI) degree programmes.

Course Organiser for "Integrated Biomedical Science 4 (IBMS4)" and "Future Perspectives" 4th year courses.

Open to PhD supervision enquiries?

Yes

Current PhD students supervised

Natasha Arzoo (PhD Student - Co-Supervised by Dr. Robert Young (Usher Institute, UoE) [Pakistan HEC Scholarship]

Honglin Yu (PhD Student ZJE Institute, China - Co-Supervisor with Dr. Di Chen (ZJE Institute)

Qizhe Shao (PhD Student ZJE Institute, China - Co-Supervisor with Dr. Di Chen (ZJE Institute)

Junping Shi (PhD Student ZJE Institute, China - Co-Supervisor with Dr. Xianghua Li (ZJE Institute) and Dr. Robert Young (Usher Institute, UoE)

Hongling Liu (PhD Student - Co-Supervisor with Prof. Nik Morton (PI) (UoE/Nottingham-Trent University), Prof. Kei Sakamoto (CBMR, Uni. Copenhagen)

Triin Ounapuu (PhD Student - Co-Supervisor with Prof. Nicola Gray (PI))

Past PhD students supervised

Shiyang He (MSc)

Ana Ingels (MSc)

Saidiburkhaniddin  Adikhanov (MSc)

Lara Scheer (MSc)

Yan Xu (MSc)

Yanjing Zhao (MSc)

 

Co-Supervised with Prof. Nicola Gray:

Mathias Lorbeer (PhD)

Hristina Gyurova (PhD)

Tajekesa Blee (PhD)

Lenka Hrabalkova (PhD)

Jessica Scanlon (PhD)

Sarah Howard (MSc)

Maria Casacao (MSc)

Huanting Chi (MSc)

Emily Walshe (MSc)

Melina Michael (BSc)

Rachael Smith (BSc)

Research summary

I am fascinated by the molecular 'circuitry' that underpins a cell's ability to produce all the proteins it requires for its viability and correct function. Without this 'circuitry' there would be nothing to ensure that proteins are made at the right time, in the correct location and in the correct amounts, therefore it is essential for life. However, the combinations of intracellular signalling and responsive gene expression that comprise the molecular 'circuits' do not always work perfectly, e.g. due to gene mutations and/or environmental influences (such as diet) and this can lead to morbidity/disease (e.g. cancer, metabolic and cardiovascular disease, neurodegenerative disease, reproductive disorders etc.....). 

It is therefore crucial that we first determine the normal cellular mechanisms that control protein synthesis. By identifying the mechanistically-required protein and RNA factors and, critically, by delineating the way in which signals from outside and inside the cell are relayed to these factors, we build a platform from which to begin understanding how protein synthesis becomes dysregulated in disease/morbidity.

Unfortunately, vast proportions of the molecular circuitry of normal metabolic and cardiovascular health remain to be uncovered and we are therefore unable to fully understand the mechanisms by which metabolic and cardiovascular diseases arise and/or progress. We aim to change this.

Current research interests

In the lab, we take complementary approaches to deciphering post-transcriptional regulation: 1) We take a targeted approach and simultaneously work to understand i) how specific RNA-binding proteins (RBPs) function to coordinate gene expression, ii) how specific RNA-binding protein functions are regulated by post-translational modifications (such as phosphorylation, acetylation and methylation) in response to specific cellular signals and iii) what signalling pathways and effector enzymes carry out these specific post-translational modifications. 2) We take an agnostic approach and aim to elucidate the post-transcriptional molecular circuitry of disease/morbidity by identifying expression and/or post-translational modification changes in the total cellular RBP-ome and changes in the RNA-binding status of all expressed RBPs (general and substrate-specific). These are multidisciplinary investigations that require both routine and cutting-edge methodologies and expertise (e.g. site-specific post-translational modification of recombinant proteins using codon extension/unnatural amino acids, surface plasmon resonance, X-ray crystallography, quantitative mass spectrometry, RBP interactome capture) and which range from in vitro methods using purified components through to in vivo physiology……and all in between. 3) Working with key collaborators at University of Edinburgh and The Centre for Basic Metabolic Research (CBMR), University of Copenhagen, Denmark, we employ population genetics approaches combined with genome-wide gene expression dataset analyses to identify human genetic variants that directly or indirectly affect post-transcriptional regulation of gene regulatory networks underpinning cardiometabolic health and disease.

Past research interests

My previous projects have primarily centred around specific RNA-binding proteins such a Tristetraprolin (TTP) or members of the poly(A)-binding protein (PABP) family. I remain actively involved in understanding the molecular and physiological functions of PABPs and how they are regulated.

Project activity

  1. Identification and characterization of heart RNA-binding protein-mediated gene expression and its dysregulation in obesity-induced Diabetic Cardiomyopathy (DCM). (Collab. with Dr. Robert Young (Usher Institute, UoE)

  2. Quantification and mechanistic characterisation of the extensive post-transcriptional regulation underpinning adipogenesis in human health and obesity. [Collab. with Dr. Tuomas Kilpelainen (CBMR, Uni. Copenhagen), Prof. Roland Stimson (CVS, UoE) and Dr. Alex Von Kriegsheim (IGC, UoE)

Current project grants

"Identifying mRNA 3’UTR and 5’UTR region cardiometabolic GWAS variants and quantifying their effect on the post-transcriptional regulation of gene expression underpinning human adipogenesis."
Awarded amount: £21,724
British Heart Foundation REA3 Pump Prime grant

"In vivo, genome-wide identification of the post-transcriptional regulation in heart that underpins the life-course of obesity-induced diabetic cardiomyopathy."
Awarded amount: £5,000
British Heart Foundation REA3 Pump Prime grant

Past project grants

"In vivo, genome-wide identification of the post-transcriptional regulation in heart and skeletal muscle that underpins the life-course of obesity-induced diabetes and cardiovascular disease"
Awarded amount: £28,632
British Heart Foundation REA3 Pump Prime grant

“Does PABP4 control diet-induced obesity, by acting as a master regulator of metabolism-related gene expression?”
Awarded amount: £545,841
BBSRC Project Reference: BB/R004668/1 [Dec 2017 - Dec 2020]
Lead author and Co-I (PI, Prof. Nicola Gray; Co-I, Prof. Nik Morton)

"Can histone code-like 'switches' govern the multi-functionality of RNA-binding proteins?"
Awarded amount: £723,957
BBSRC Project Reference: BB/P022065/1 [Sep 2017 - Sep 2020]
Lead author/Co-Investigator (PI, Prof. Nicola Gray; Co-I, Dr. Atlanta Cook)

“Poly(A)-binding proteins highlight the importance of regulated mRNA translation and stability in determining a functional maternofetal interface”
Awarded amount: £1.4M
MRC Program Grant [2012-2017]
Joint Co-Author (PI, Prof. Nicola Gray)

View all 19 publications on Research Explorer

Organiser

Translation UK 2010: Biochemical Society Focussed meeting

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