Dr Mark Collins

School of Biosciences

Senior Lecturer in Biological Mass Spectrometry

Deputy Director of the Mass Spectrometry Centre

Dr Mark Collins
Profile picture of Dr Mark Collins
mark.collins@sheffield.ac.uk
+44 114 222 2303
Profile
  • 2019-present: Senior Lecturer, University of Sheffield
  • 2013-2018: Lecturer, University of Sheffield
  • 2011-2013: Senior Staff Scientist, Wellcome Trust Sanger Institute
  • 2005-2011: Research Associate/Staff Scientist, Wellcome Trust Sanger Institute
  • 2001-2005: PhD, Division of Neuroscience, University of Edinburgh
  • 2000-2001: Research Assistant, Centre for Liver Disease, Mater Misericordiae University Hospital, Dublin.
  • 1996-2000: BSc, Department of Biochemistry, University College Dublin
Research interests

We are interested in how proteins are regulated by post-translational modifications and how cell signalling pathways are perturbed in disease. PTMs such as phosphorylation, ubiquitination, acetylation and palmitoylation regulate overlapping and distinct aspects of protein function, but the interplay of these modifications is not well understood.

We exploit biochemical and quantitative mass spectrometry-based approaches to understand how proteins are dynamically regulated by protein synthesis and degradation and an array of post-translational modifications.

Research themes

Neuroproteomics

We have a long-standing interest in understanding how brain proteomes relate to fundamental aspects of learning and memory and how they are altered in disease. We have been at the forefront of proteomic studies of synapses from the interrogation of the composition of pre and post-synaptic fractions to the characterisation of postsynaptic glutamate receptor associated protein complexes and their regulation by post-translational modifications.

Figure 1

We are currently investigating how the synapse proteome is regulated by palmitoylation and lysine acetylation; important PTMs that regulate association of proteins with pre and post synaptic membranes and protein stability, respectively.

We are together with our collaborators investigating the composition of synapse proteomes in several mouse models of disease and human iPS cell derived neuronal models of disease including Schizophrenia, Alzheimer's disease and ALS. Furthermore, we are currently conducting clinical proteomics studies of ALS patient cohorts to identify biomarkers of oxidative stress to enable the action of therapeutics to be assessed.

Regulation of membrane protein function by S-acylation (Palmitoylation)

Palmitoylation, the only known reversible lipid modification of proteins, is a critical regulator of protein trafficking, stability and signalling and is important for all cell types, and organisms from yeast to humans.

Proteins can be palmitoylated by a family of 23 protein acyl transferases (PATs) in humans and many of these enzymes have been shown to regulate important aspects of cell biology and in particular in neuronal cells in the brain where palmitoylation of receptors and associated proteins are essential for communication between brain cells and therefore functions such as learning and memory.

Indeed, several PATs have been implicated in the pathophysiology of neurological disorders from Huntington’s disease to intellectual disability and schizophrenia and well as other diseases such as diabetes and cancer.

The identification of determinants of substrate specificity of palmitoyl acyltransferases is an important goal toward understanding how palmitoylation regulates cell function. Development of strategies to enrich, identify and quantify proteins and PTMs is also a major focus of research in our lab.

Figure 2

Perturbed signalling pathways in neurodegenerative diseases

Motor Neurone Disease or Amyotrophic lateral sclerosis (ALS) is a disorder that results in fatal paralysis within a few years of symptom onset. Defects in a growing list of genes are associated with the development of ALS/MND.

Many of these gene defects result in the accumulation of aggregates in cells of patients with ALS and these aggregates are believed to cause neurons to die, resulting in the symptoms of the disease.

Recently, a number of large exome sequencing studies of ALS patients have independently identified several loss of function mutations in protein kinases but it is not known how dysregulation of these kinases might contribute to development of disease.

We are using protein biochemistry, immunofluorescence microscopy and  phosphoproteomic approaches to understand how human mutations lead to molecular and cellular changes that contribute to to the pathogenesis of ALS.

Figure 3

Mass spectrometry-based proteomics

The key enabling technology for our research is shotgun proteomics; in which protein samples (whole cell lysates, organelles, protein complexes etc.) are digested with into peptides, separated using nanoflow chromatography and analysed using high-resolution tandem mass spectrometry (Faculty of Science Mass Spectrometry Facility). This approach permits unbiased, quantitative analysis of protein levels and PTMs, with unrivalled accuracy and sensitivity.

Figure 4

We exploit affinity purification and proximity labelling strategies to purify and characterise multiprotein complexes formed by protein kinases and palmitoyl-acyltransferases to identify their substrates as well as regulatory proteins that determine substrate specificity or target these enzymes to different subcellular compartments or membrane microdomains.

Collaborations

Prof Shaun Cowley (University of Leicester)

Dr Daniel Humphreys (University of Sheffield)

Prof Dave Kelly (University of Sheffield)

Dr Stéphane Mesnage (University of Sheffield)

Dr Andrew Peden (University of Sheffield)

Dr Richard Mead (University of Sheffield)

Prof Pamela Shaw (University of Sheffield)

Publications

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Journal articles

All publications

Journal articles

Chapters

Conference proceedings papers

Preprints

Research group

PhD students

  • Hatoon Alamri
  • Weronika Buczek
  • Ella Hudson*
  • Sam Lewin*
  • Ola Shehata*
  • Salma Srour*
  • Ashley Griffin*
  • Ankur Patel*
  • Nick Verber*
  • Jorge Miguel Ferreira*

*Co-supervisor

Grants
  • BBSRC
  • MRC
  • Weston Park Hospital Cancer Charity
  • Royal Society
Teaching activities

Undergraduate and postgraduate taught modules

Undergraduate:

  • BMS109 Cell & Molecular
  • Level 3 Practical and Dissertation Modules         

Doctoral Development Programme

  • BMS6007: Mass Spectrometry-based Proteomics and Metabolomics Course (Director)
Professional activities and memberships
  • Guest Editor at Frontiers in Molecular Neuroscience
  • Fellow of the Higher Education Academy (2016)
  • Peer reviewer for scientific journals and grant-awarding bodies
Opportunities

I welcome applications from international students who are self-funded or have (or are applying for) a government scholarship.

We advertise PhD opportunities (Funded or Self-Funded) on FindAPhD.com

For further information and details of other projects on offer, please see the department PhD Opportunities page.

Links

Neuroscience Institute