New tools for immunopeptidomics (Industry Academia Alliance PhD scholarship available)

An opportunity for an outstanding PhD candidate to undertake a collaborative project between Industry and Monash University. The project: The use of peptides to infer protein expression is very familiar to all of those who undertake bottom-up proteomics studies of cells, tissues and fluids. Remarkably, an analogous process is used by the immune system to report on the presence of infectious micro-organisms, malignancy and other abnormalities within the body. This process known as antigen processing and presentation relies on the selection and presentation of peptides on the surface of cells as a bound complex with Major Histocompatibility Complex (MHC) molecules. The isolation and characterisation of these MHC-bound peptides, predominantly through the use of liquid chromatography and mass spectrometry, has been coined immunopeptidomics. Immunopeptidomics as a field has rapidly matured in the past decade and has moved from the domain of just a handful of specialised laboratories to now being more generally applied by the proteomics and immunology communities. Protocols for isolating peptide-MHC complexes under near native conditions and the analysis of the bound peptide cargo by LC-MS/MS have been refined alongside tremendous developments in instrumentation. This has facilitated the analysis of tens of thousands of peptides using this technique. With such information rich and deep datasets reporting on peptide epitope display by a variety of different cell types and tissues, profound insights into fundamental mechanisms of antigen presentation have been gained; both in the steady state and how this state may be perturbed by various environmental or infectious agents. The maturation of immunopeptidomics has also facilitated the identification of T cell epitopes in a variety of diseases including autoimmunity, cancer and infectious disease. It has revealed the critical role that posttranslational modification has in the immune response and allowed enumeration of specific epitopes with great accuracy and precision. This project will explore new data acquisition strategies, leveraging multiple fragmentation modalities (e.g. EtHCD, HCD, CID, ECD) and ion mobility measurements (CCS, CoV) to generate large multidimensional immunopeptidomic datasets to train the next generation of bioinformatic software. This will include development of novel machine learning approaches to improve de novo sequencing, precise PTM mapping and site assignment and direct identification of cancer neoantigens. The industry-academia alliance: Since 2017, the Purcell laboratory has collaborated with Bioinformatic Solutions to improve the bioinformatic interrogation of LC-MS/MS data form immunopeptidomics data sets. Purcell Laboratory, Department of Biochemistry & Infection and Immunity Program, Biomedicine Discovery Institute is located at the Clayton Campus, Monash University, Australia. The laboratory uses stateof-the-art biochemical and immunological approaches to identify targets of immunity across a broad array of human diseases and disorders see -www.med.monash.edu.au/biochem/labs/purcell. Bioinformatic Solutions was founded in March 2000 in Waterloo, Ontario, Canada and is well known for the development of the software, PEAKS, used to identify and quantify proteins in very complex biological samples with LC-MS. BSI are continually involved in research and the advancement of algorithms to provide solutions to facilitate the understanding of life sciences and answer important biological questions. BSI closely collaborate with their users and experts worldwide to simultaneously help them with their research and shape future PEAKS products. See - http://www.bioinfor.com/ Applicants should hold a First class BSc (Hons) or MSc (Research) in Biochemistry or Immunology. Experience in a mass spectrometry, bioinformatics and/or mammalian cell culture would be an advantage. A generous Industry funded stipend is offered which includes travel funding to visit BSI in Canada. Interested candidates should contact Prof Tony Purcell (Anthony.purcell@monash.edu) with a full CV and their expression of interest.