Matthew Brook

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

  • Centre for Cardiovascular Science
  • Centre for Reproductive Health
  • Biomedical Sciences

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)

Undergraduate teaching

Assistant Professor at Zhejiang University-University of Edinburgh (ZJE) Institute, lecturing on the Biomedical Sciences Joint Honours degree program. Course Organiser for "Integrated Biomedical Science 4 (IBMS4)", 4th year course.

Open to PhD supervision enquiries?

Yes

Current PhD students supervised

Mathias Lorbeer (PhD student)

Hristina Gyurova (PhD Student)

Past PhD students supervised

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 two 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.

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.

Current project grants

"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)

“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)

Past project grants

“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

This article was published on