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Croft Lab research

CollaborationsStudent research projects | Publications

About Dr Nathan Croft

Dr Croft awarded his PhD from the University of Birmingham (UK) in 2009, studying immune evasion by Epstein-Barr virus. Thereafter, he joined the group of Professor Tony Purcell at the University of Melbourne, transitioning to Monash University with the rest of Professor Purcell’s team in 2012. Dr Croft’s research is focused on understanding how different aspects of the MHC antigen processing pathway impact upon T cell immunity to pathogens and tumours. He is particularly interested in how the abundance of MHC-peptides plays a role in driving the magnitude and efficacy of T cell responses. Over the last eight years, Dr Croft has developed the methodology to study peptide abundance by highly sensitive mass spectrometry. In conjunction with this work, he is actively engaged in mapping the peptide repertoires of healthy and pathogen-infected cell lines, as well as cells and tissues of tumour origin. Together this work strives to develop novel bioinformatics and data repositories that will model and predict the generation of peptide epitopes and their potential immunogenicity.

Dr Croft is currently a Chief Investigator on an NHMRC Project Grant focusing on recognition of virus-infected cells by T cells.


Our research

Current projects

Recognition of virus-infected cells by T cells

The immune system’s T cells are able to survey the contents of cells via scrutiny of peptides bound to major histocompatibility complex (MHC) molecules presented at the cell surface. These peptides derive from processing of intra- and extra-cellular proteins, and the array of presented peptide-MHC is collectively termed the immunopeptidome. The display of virus-derived peptides on infected cells therefore alerts T cells to infection. Our group is interested in comprehensively understanding viral peptide-MHC display through detailed analysis of the diversity and immunogenicity of CD8+ T cell targets to complex viral pathogens. We are also enumerating the kinetics of antigen presentation from virus-infected lymphoid and mouse tissue, towards correlating with T cell priming occurring within the same individual.

Defining immunogenicity through systems immunology

There is currently a significant challenge in predicting the immunogenicity of any given peptide-MHC molecule, be it in mouse models or humans, or in the context of infection or cancer. This is particulary important when considering personalised therapy, where a peptide may be presented and immunogenic in one individual, but not in another. A multitude of factors during antigen processing and presentation likely govern resultant immunogenicity (see Figure 1), but delineating their respective contributions has remained elusive. Our group aims to provide a holistic understanding of these processes through quantitative measurements.

Figure 1 – Steps in antigen processing and presentation that shape immunogenicity. PTM, post-translational modification; TCR, T cell receport;
MHC, major histocompatibility complex; TAP, transporter associated with antigen processing; PLC, peptide loading complex.

Visit Dr Croft's Monash research profile to see a full listing of current projects.

Techniques/expertise

  • Proteomics
  • Mass spectrometry (data-dependent, data-independent and targeted modalities)
  • Liquid chromatography
  • Immunopeptidomics
  • Immunoprecipitation
  • Flow cytometry

Disease models

  • Influenza infection
  • Autoimmunity
  • Melanoma

Collaborations

We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

Professor Tony (Anthony) Purcell (Monash University)
Professor Nicole La Gruta (Monash University)
Professor David Tscharke (Australian National University)
Professor Paul Hertzog (Hudson Institute)
Paul Thomas, PhD (St Jude Children’s Hospital, Memphis, USA)


Student research projects

The Croft Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Supervisor Connect to explore the projects currently available in our Lab.