Currently Open Positions

Kolanus - Mintern collaborative project

Melbourne subproject

Title: Identifying new molecular machinery for dendritic cell vaccination

Melbourne supervisor: A/Prof Justine Mintern; Bio21 Institute, University of Melbourne

Bonn supervisor: Prof Waldemar Kolanus; Life and Medical Sciences Institute, University of Bonn

While vaccines are in use worldwide, for many pathogens we lack the ability to eradicate them by vaccination with ensuing uncontrolled disease. As evidenced with the recent pandemic, this can result in devastation worldwide. Vaccines also have the potential to prevent and treat cancer, with this emerging as a clinical reality. Vaccine design must be advanced, and to do so, we require a more comprehensive understanding of the cell biology and machinery involved. A key objective in vaccine biology is to identify how the machinery inside immune cells critically impacts immune outcomes. This machinery is the target for future therapeutic intervention and manipulation in settings of immunotherapy. This project will use CRISPR/Cas9 methodology, together with sophisticated imaging technology, to investigate how specific molecular machinery regulates dendritic cell immunity. Dendritic cells are immune cells that survey tissues to capture antigen. Dendritic cell presentation of antigen is the first step in adaptive immunity and is a critical response for vaccination. The Melbourne aspect of this project aims to identify molecular pathways controlling trafficking of dendritic cells. The Mintern lab has developed unique genetic screens to identify new molecular pathways in dendritic cells. Once the molecular machinery is identified and validated, these genes will be targeted and tested in mouse models of vaccination and immunotherapy. The Mintern laboratory has several novel models of vaccination against infection and cancer. The project will continue in the Kolanus laboratory at Bonn University. The Kolanus laboratory uses sophisticated imaging technology to measure detailed parameters of dendritic cell trafficking in real time. This project will generate fundamental insights into dendritic cell biology that will inform the development of new therapeutics to enhance immunotherapy and vaccination.

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Brooks - Schlee collaborative project

Melbourne subproject

Title: Understanding natural killer cell responses to bacterial infection

Melbourne supervisor: Prof Andrew Brooks, Doherty Institute for Infection and Immunity, University of Melbourne

Bonn supervisor: Prof Martin Schlee, Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn

Natural killer (NK) cells are an important component of the innate immune system. Upon activation, NK cells have the potential to lyse damaged or infected cells as well as to secrete an array of inflammatory cytokines and chemokines which may act to both control infection and/or recruit cells to the site of activation. Unlike other major lymphocyte subsets which typically sense infection or cancer through the engagement of a clonotypic receptor, the activation of NK cells is regulated by signals received from a diverse array of both activating and inhibitory receptors. Since the cytotoxic response of NK cells requires recognition of host proteins, the majority of research has focussed on their response to either transformed or virus-infected cells. However, many bacteria also have the capacity to infect mammalian cells raising the potential that NK cells may impact their pathogenesis, particularly through the secretion of cytokines such as interferon-gamma. This project aims to define the molecular mechanisms used by NK cells to sense bacterial infection and explore the potential of bacteria to subvert these processes. The Melbourne component of the project will assess how distinct intracellular bacterial infections stimulate or evade NK cell responses. The Brooks laboratory has expertise in NK cell receptor biology and has developed CRISPR/Cas9 -based methods to use gene editing to define the key mechanisms responsible for NK cell activation in diverse settings. The Schlee laboratory at Bonn University uses sophisticated approaches to define how cells sense foreign nucleic acids to better understand the nature of the very initial response to infection. Using these same models of bacterial infection, the Bonn arm of the project will define how these distinct infections interact with the diverse array of intracellular nucleic acid sensing receptors and then how this impacts crosstalk between the infected cell and NK cells. Understanding of the pathways by which bacterial infection modulates cross talk between infected cells and NK cells may lead to the identification of novel ways to enhance NK cell responses not only to bacteria but to viral infection and cancer as well as providing a pathway to develop therapeutic approaches to effectively manipulate the innate immune response. The first two years of project will be based in Melbourne before shifting to Bonn for a further 12 months.

Please visit the relevant links for more information on:

Förster - Villadangos collaborative project

Bonn subproject

Title: Impact of the chemokines CCL17 and CCL22 in the development of infectious immunoparalysis

Bonn supervisor: Prof Dr Irmgard Förster, Immunology and Environment, LIMES Institute, Bonn, Germany

Melbourne supervisor: Prof Dr José Villadangos, Dept. Microbiology and Immunology, The Peter Doherty Institute, and Bio 21, Dept. Biochemistry and Molecular Biology, Melbourne, Australia

Severe infections often cause a long-lasting immunosuppression rendering the host susceptible for secondary infections. This immune paralysis might be regulated by changes in antigen presenting cells inducing an aberrant T cell response in response to the pathogen. We demonstrated that dendritic cells (DC) and macrophages express the chemokines CCL17 and CCL22 to regulate their interaction with T cells. Whereas CCL17 exerts pro-inflammatory functions and is induced by Toll-like receptor (TLR) stimulation, CCL22 rather appears to play an immunoregulatory role. Together with the Strugnell lab, we demonstrated that combined deficiency of CCL17 and CCL22 strongly enhances vaccination efficiency in a mouse model of Salmonella infection leading to a significant reduction in activated regulatory T cells (Treg). We will now focus on the role of these chemokines in a model of immune paralysis established in the Villadangos lab. Here, myeloid cells (alveolar macrophages and dendritic cells) are epigenetically and metabolically altered by the local inflammatory environment, which favors the accumulation of Treg, rendering the organism more susceptible to secondary infections. In addition, injection of CpG oligonucleotides prior to Salmonellainfection leads to a much higher bacterial burden in mice, which might also resemble immune paralysis. We want to characterize the myeloid cells involved in the altered immune response in the Salmonella model. We intend to investigate how the reprogramming of myeloid cells in both models is altered and will precisely analyse the epigenetic and metabolic state of these paralyzed myeloid cells. In addition, we want to unravel whether CCL17 and CCL22 influence activation and differentiation of these myeloid cells and impact activation and recruitment of T cells and thereby affect adaptive immune responses to infection. If CCL17 and/or CCL22 negatively regulates T cell responses, we plan to apply recently generated aptamer reagents to therapeutically block these chemokines.

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Wilhelm - L.Mackay collaborative project

Bonn subproject

Title: Control of Barrier Immunology by Regular Exercise

Bonn supervisor: Prof Christoph Wilhelm, Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn

Melbourne supervisor: Prof Laura Mackay, Doherty Institute for Infection and Immunity, University of Melbourne

Masters - Geyer collaborative project

Melbourne subproject

Title: Investigation of a novel cell death protein

Melbourne supervisor: A/Prof Seth Masters, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne

Bonn supervisor: Prof Matthias Geyer, Institute of Structural Biology, University of Bonn

Taking advantage of recent advances in the prediction of protein folds we have identified an uncharacterised protein that appears to be involved in cell death. This project will use unbiased approaches to determine the signalling pathways that the protein regulates and precisely how it may function to regulate cell death in contexts such as cancer, inflammation and infection. This could be related to programmed cell death such as apoptosis, necroptosis or the inflammasome and pyroptosis. Starting with studies in the Masters laboratory (Australia) we will make cell line models with CRISPR deletion or overexpression of the protein and/or its relevant domains, and interrogate them using the world class medical research techniques available at WEHI. The project will then move for the final year of the PhD to the Geyer laboratory (Germany) for biophysical and structural studies of the heretofore uncharacterised protein. Through this work we expect to determine the cellular and biochemical role of the protein, which may provide opportunities for drug discovery and an improved understanding of fundamental biological process relevant to human disease.

Academic entry requirements:
We welcome applications from all countries and nationalities. To be eligible for entry you are expected to have successfully completed your BSc and MSc degree (or close to completion) in Biology, Immunology, Molecular Biology, Biochemistry, or related fields and achieved an overall average of greater than 80%. This is a minimum entry requirement and serves as a guide only. You are also required to have completed a research project that accounts to at least 25% of one year of study and must possess excellent English language skills. Additional qualifications and/or experience in a relevant field, reference reports and scientific publications will also be taken into consideration.

Funding includes:
- Stipend $32,400 per year pro rata (2022 full-time study rate, includes sick pay, maternity and parental leave), for up to 3 years with a possible 6-month extension.
- 100% fee remission up to $110,000
- One-off relocation grant of up to AUS$3,000 for international students relocating to Melbourne
- Insurance
- Travel costs for exchange to Bonn

How to apply:
Candidates who meet the minimum entry requirements are asked to submit the following documents via email:
1. Letter of motivation
2. CV in German or Englisch language
3. Electronic copy of your full BSc and MSc University transcripts (or equivalent) in German or English language
4. Evidence of English language competency (study abroad, IELTS, TOEFL, or similar)

Contact/application to: annabelle.blum@unimelb.edu.au