Membrane trafficking at atomic resolution

 

Our work is focused on understanding how membrane-associated protein complexes are assembled to control receptor transport and the homeostasis of endocytic organelles.

We are primarily interested in the fundamental molecular mechanisms that underpin these processes in healthy cells.

But we also hope that by better understanding how these essential protein machineries function we may be able to develop drugs or therapies that target them in various disease.

Most notably the dysfunction of membrane trafficking is a common hallmark of neurodegenerative disorders including Parkinson’s and Alzheimer’s Diseases.

Tubule structure

Structure of membrane assembled Retromer with the SNX-BAR protein Vps5 determined by cryoelectron microscopy (Kovtun, Leneva et al., 2018, Nature). 

 

Retromer protein complex

Group leader

Professor Brett Collins

Professor Brett Collins

Group Leader, Cell and Developmental Biology

  +61 7 334 62043
  b.collins@imb.uq.edu.au
  UQ Researcher Profile

Our approach

Our lab is focused on the study of protein structures, using methods including X-ray crystallography, cryo electron microscopy (cryoEM), and nuclear magnetic resonance spectroscopy (NMR). We believe however, that it is only when placed within a framework of experimental validation in cellular and in vivo systems that the power of structural biology can be fully realised.

This scientific philosophy underpins all of our research and is the driving motivation for building collaborations with outstanding cell biology labs in Australia and internationally. This integrated multi-disciplinary approach underpins our ongoing studies of membrane trafficking coat complexes, combining X-ray crystallographic structure determination, biochemical characterisation of protein interactions and cell biological assays for protein function.

The molecular insights gained from such an approach also provides the essential platform for drug design and screening aimed at disrupting or enhancing these cellular pathways.

Research areas

Peripheral membrane proteins are essential for cellular trafficking and membrane remodelling, and have emerged as key determinants in many human disorders, including Alzheimer’s and Parkinson’s diseases, cancer, epilepsy and muscular dystrophy. This provides new opportunities for treating these conditions, but requires a much more detailed molecular understanding before such goals can be realised. Using cutting-edge structural, molecular and cellular approaches our lab aims to determine how these proteins control essential processes of cellular homeostasis, hormonal signaling, tissue morphogenesis, and neurosecretion in health and disease. 

  1. The Retromer complex in endosomal sorting and neurodegeneration

    The Retromer complex is a peripheral membrane protein assembly that is essential for endosomal trafficking and is mutated in neurodegenerative diseases including Alzheimer’s and Parkinson’s. Our lab has made important contributions to the molecular understanding of retromer function and continues to use the techniques of X-ray crystallography and Electron Microscopy to study the principles that govern its assembly and dysfunction. 

  2. Intracellular trafficking and membrane regulation by Sorting Nexins (SNXs)

    Sorting nexins are a large and diverse family of proteins with various roles in intracellular membrane transport and cell signalling. Their dysfunction is implicated in diseases including cancer, inflammation, genetic disorders and Alzheimer's disease, and they are emerging as therapeutic targets in these disorders. We aim to discover their mechanisms of action and to determine their potential for therapeutic development. 

  3. The Commander protein complex in endosomal homeostasis

    Distantly related to the Retromer protein machinery, Commander is a recently identified endosome-associated protein complex. It plays important roles in endosomal sorting of cargos including integrins and lipoprotein receptors and rare mutations in Commander proteins lead to X-linked intellectual disability. We aim to capture a complete snapshot of how the many Commander subunits are integrated into a functional complex.

  4. Caveola biogenesis and the role of the cavin proteins

    Caveolae are ~50 nm bud-like structures on the plasma membrane, with multiple roles in signal transduction, endocytosis and as sensors of membrane stress. In collaboration with Prof. Rob Partin (IMB, UQ) we aim to determine the molecular principles that govern the assembly of these critical protein-coated membrane vesicles. 

  5. Regulation of neurosecretion by SNAREs and Munc18

    SNARE-mediated membrane fusion is required for regulated exocytosis and is critical in many cellular processes including neurosecretion, insulin secretion, immune responses and inflammation. The assembly of all SNARE complexes during membrane fusion is very tightly regulated by proteins of the Sec/Munc (SM) protein family that bind primarily to the syntaxin SNARE subunits and together with Prof. Fred Meunier (QBI, UQ) we are attempting to define the pathways and molecular interactions of SNARE and SM proteins that regulate neuronal synaptic function. 

Our team

Group Leader

  • Professor Brett Collins

    Group Leader, Cell and Developmental Biology Division
    Professorial Research Fellow - GL
    Institute for Molecular Bioscience

Researchers

Postdoctoral Researchers

Masters Students

Research excellence

$1.3 billion+ commercial investment attracted to IMB research
1454 international collaborators
 
385 original publications in 2020
 
$28M in research funding last calendar year
 
20%+ of patent families at UQ are derived from IMB research
100% of donations go to the cause
 

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