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Associate Professor Andrew Sutherland-Smith staff profile picture

Contact details +64 (06) 356 9099  ext. 84701

Associate Professor Andrew Sutherland-Smith PhD

Associate Professor

School of Fundamental Sciences

My research interests are in protein structure & function, biochemistry, molecular biology and cell biology. My lab is particularly focused on understanding the relationship of protein structure to protein function, and the implications of this relationship in both biomedical and evolutionary contexts. My teaching contributions are into the BSc (biochemistry and genetics) and BVSc programs. Before taking a faculty position at Massey University I was a postdoctoral fellow at the Medical Research Council Laboratory of Molecular Biology, Cambridge UK.

Professional

Contact details

  • Ph: +6463569099
    Location: ScC403b, Science Tower C
    Campus: Manawatu

Qualifications

  • Doctor of Philosophy - Massey University (2003)

Research Expertise

Research Interests

Our lab is focused on understanding the relationship of protein structure with protein function, and the implications of this relationship in both biomedical and evolutionary contexts.

Defining the protein structure-function relationship is very informative in understanding molecular mechanisms of inherited genetic diseases where often only a single amino acid change in a protein, caused by just a single nucleotide change in gene sequence, results in altered cellular events leading to human diseases. We apply  a structural biology/biochemical approach to understanding the effects of missense mutation on proteins associated with muscle, skeletal and neurological diseases. Specifically we are interested in the structure and function of the filamin family of proteins, associated with neurological, skeletal and muscle disorders, and of dystrophin the protein mutated in Duchenne and Becker Muscular Dystrophies. Furthermore we are interested in functionally comparing dystrophin to its homologous protein, utrophin, which has been proposed as a therapeutic replacement protein for defective dystrophin function. The study of inherited human disorders provides crucial insights into normal cellular events as well as illuminating disease mechanisms. We also are very interested in understanding functional mechanisms of key glucokinase enzymes and muscle signaling proteins.

Sequence comparison has been the traditional methods of establishing genetic evolutionary relationship between proteins. Evolutionary structural comparisons are more difficult to perform but are potentially far more information rich as it is protein structure that is the functional selectable evolutionary unit rather than the gene or protein sequence. We have taken a structural-bioinformatic approach to examining the evolutionary distribution of the Major Vault Protein and its phylogenetic relationship to the last eukaryotic common ancestor, and are now looking at other gene families. Our research group also has interests in understanding the functional and evolutionary relationships between bacterial and archaeal cell wall synthetic enzymes using experimental structure and function approaches.

Our lab uses structural biology, in vitro biochemistry, cell biology and bioinformatics methods to investigate these research areas. 

Research Opportunities

  • PhD Scholarships (Massey University)  (01/07/2014) Massey University offers PhD scholarships to students from all nationalities. If you are interested in our research and hold a first class (or 2-1) MSc/BSc(Hons) degree (or equivalent) please enquire.

Thematics

Health and Well-being

Area of Expertise

Field of research codes
Biochemistry and Cell Biology (060100): Bioinformatics (060102): Biological Sciences (060000): Cellular Interactions (incl. Adhesion, Matrix, Cell Wall) (060106): Enzymes (060107): Evolutionary Biology (060300): Genetics (060400): Molecular Evolution (060409): Structural Biology (incl. Macromolecular Modelling) (060112)

Keywords

Biochemistry, Molecular Biology, Cell Biology, Structural Biology, Protein Structure and Function, Enzymes, Biomedical Research, X-ray crystallography, Protein Assays, Protein Purification, Cytoskeleton, Actin, Filamin, Dystrophin, Utrophin, 

Research Projects

Summary of Research Projects

Position Current Completed
Project Leader 1 17

Completed Projects

Project Title: Stretching Protein Springs: How do cells respond to force

The transformation of cell type, the control of cell shape and cell movement are essential processes for human development. Remodelling of the cytoskeleton, the internal scaffold of cells, is central to these cellular capabilities. Through our previous genetic studies of a range of human diseases, characterised by skeletal malformations, we have found mutations within the filamin family of proteins. The filamins bind components of the cytoskeleton participating in tissue and organ formation in humans. How these disease-associated mutations affect human development is unclear to date. The idea we will explore is that filamin acts as a spring-like force-sensing protein to measure force directly applied to cells and to gauge the stiffness of the surface to which cells are attached. We propose that the mutations found in patients affect tensioning of the filamin spring, causing abnormal cell responses and ultimately defective tissue development. We will investigate this hypothesis by comparing the elasticity and binding strength of filamin, both with and without the disease-associated mutations, in isolated cytoskeletal filament networks. We will also examine cellular effects by comparing the different responses of normal and patient cells to applied force and how they behave on surfaces of varying stiffness.
Read Project Description Hide Project Description

Date Range: 2011 - 2014

Funding Body: Marsden Fund - Full

Project Team:

Research Outputs

Consultancy and Languages

Consultancy

  • 2011 - Public Library of Science (PLoS) One Journal
    Academic Editor
  • 2011 - Biomedical Central (BMC) Research Notes
    Editorial Board

Teaching and Supervision

Teaching Statement

Protein Structure and Function

Protein Biochemistry

Biochemistry

Biochemistry for Technology

Molecular Cell Biology

Biochemistry for Veterinary Science

Genome Analysis

Research Methods

Advanced Topics in Molecular Biology

Advanced Topics in Biochemistry

Biophysics

Genes and Gene Expression

Courses Coordinated

Summary of Doctoral Supervision

Position Current Completed
Supervisor 1 5
Co-supervisor 4 7

Current Doctoral Supervision

Supervisor of:

  • Danielle Visser - Doctor of Philosophy
    Structural and functional analysis of viral endopeptidases PeiW and PeiP: possible allies against methane production in ruminants

Co-supervisor of:

  • Wei Jun Tan - Doctor of Philosophy
    Investigating the role of HDAC4 in Drosophila brain development and memory formation.
  • Rayen Leon - Doctor of Philosophy
    Characterisation of the filamentous bacteriophage end-caps
  • Jeremy Stephens - Doctor of Philosophy
    Establishing systems to characterise MH pathogenic RyR1 variants
  • Jin Xiang Wong - Doctor of Philosophy
    Modular Functionalization of Engineered Polyhydroxyalkanoate Scaffolds

Completed Doctoral Supervision

Supervisor of:

  • 2019 - Bishwa Subedi - Doctor of Philosophy
    Structural and functional studies of pseudomurein peptide ligases in methanogenic archaea
  • 2014 - Jan Richter - Doctor of Philosophy
    Structure and function of the eukaryotic ADP-dependent glucokinase
  • 2013 - Muralidharan Muthu - Doctor of Philosophy
    Structural and Biochemical Characterisation of Utrophin and Dystrophin Spectrin Repeat Domains
  • 2010 - Carlene Starck - Doctor of Philosophy
    The human myostatin precursor protein: Structure, function and amyloid formation: Implications for the muscle wastage disease sporadic inclusion body myositis
  • 2009 - Alice Clark - Doctor of Philosophy
    The filamin A actin binding domain structure and function: Implications for a gain-of-function mechanism for the otopalatodigital syndrome spectrum disorders

Co-supervisor of:

  • 2020 - Xi Xu - Doctor of Philosophy
    Regulation of postharvest inflorescence senescence in Arabidopsis thaliana
  • 2016 - Toni Daly - Doctor of Philosophy
    Beyond BLASTing: Ribonucleoprotein evolution via structural prediction and ancestral sequence reconstruction
  • 2013 - Cornelia Roesl - Doctor of Philosophy
    Functional and structural characterisation of the Malignant Hyperthermia associated RYR1 mutation R2452W
  • 2012 - Martina Dautel - Doctor of Philosophy
    Shedding light on the link between the actin cytoskeleton and stress response in Saccharomyces cerevisiae
  • 2010 - Martin Schwalbe - Doctor of Philosophy
    Intrinsic disorder and coiled coil formation in prostate apoptosis response factor-4 (Par-4)
  • 2010 - Nicholas Bennett - Doctor of Philosophy
    Unlocking the M13 (fl and fd) virion: Investigation into the role of the pIII C-domain of F specific filamentous bacteriophage in infection
  • 2010 - Jolyon Claridge - Doctor of Philosophy
    Characterisation of an interaction involved in viral replication

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