Currently Open Positions

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.

Please visit the relevant links for more information on:

• Academic entry requirements
• Funding for Melbourne-based positions
• How to apply

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:

• Academic entry requirements
• Funding for Melbourne-based positions
• How to apply

Despite vaccination and antibiotics, infections leading to pulmonary damage and pneumonia are amongst the top four killers worldwide. Although much is known about the role of innate and adaptive immunity in fighting pneumonia, much less is known about regulatory circuits controlling the activity of immune cells resulting in pathogen clearance. We aim at untangling these interactions by combining the long-standing expertise on cellular immunity, lung infections and microbiology in the laboratories of the Bonn and Melbourne supervisors. Recently, we have identified a novel cross-talk between lung epithelial cells and neutrophils resulting in increased bactericidal activity of the later and accelerated pathogen clearance. In this funding period, we want to extend on those finding to understand the precise cellular and molecular interactions in this stroma-immune cell crosstalk. For this, we will employ state-of-the-art technologies such as single-cell mRNA sequencing, advance imaging, high-dimensional flow cytometry, proteomics, metabolomics, genetically-modified models, organoid cultures and diverse cellular assays. This project will provide fundamental insight to understand immunity against bacterial and viral lung pathogens that may provide the basis for novel therapies in human pneumonia.
 

Please visit the relevant links for more information on:

• Academic entry requirements
• Funding for Bonn-based positions
• How to apply

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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• Academic entry requirements
• Funding for Bonn-based positions
• How to apply

A major societal challenge over the last decades in the Western World and an important aspect of modern living is the reduced amount of physical movement combined with changes in dietary nutrition, leading to an increased incidence in chronic inflammation. Many inflammatory disorders manifest at barrier surfaces: allergies and asthma affect the lung, psoriasis affects the skin, while inflammatory bowel disease (IBD) results in chronic inflammation of the intestinal epithelium. Such inflammatory conditions are mainly driven by cytokine secretion of innate lymphoid cells (ILCs) and T helper cells. However, the etiology of these diseases is poorly understood, but is likely associated with changes in life-style coinciding with westernization, such as an overall increase in hygiene, abundant nutritional uptake, together with a reduced amount of physical activity. This project aims to unravel the effects of voluntary wheel running (VWR) in mice on the functionality of barrier immunology with particular focus on the regulation of metabolic pathways driving innate immune cell recruitment and T cell activation, differentiation and memory function. Based on exercise-induced changes in the host immune system we aim to elucidate to which extent a lack of exercise might on the one hand contribute to chronic inflammatory conditions (Crohn’s Disease, psoriasis or asthma), but also bacterial (Salmonella typhimurium) or viral (Influenza) infections. With our results we aim to assess whether exercise or an exercise-induced factor may be used as a potent therapeutic strategy in the future. The project will benefit from the complementary expertise of the Mackay lab in Melbourne (tissue resident T memory cells, bacterial and viral skin infection in in vivo models) and the Wilhelm lab in Bonn (dietary immunology, immunometabolism and barrier immunology).

Please visit the relevant links for more information on:

• Academic entry requirements
• Funding for Bonn-based positions
• How to apply