NHMRC and ARC Grant success in 2024

Lung cancer is the leading cause of cancer related deaths. New drugs that bolster the ability of the patient’s own immune system to fight their cancer has revolutionized treatment. However, despite early promise, the response to these immunotherapies in lung cancer has been underwhelming. We will undertake a comprehensive characterization of the immune-lung tumour interactions in vivo, and test modulating drugs in a step towards improve patient outcomes.

Some disease causing bacteria are able to replicate within human cells leading to life-threatening infections. The response of the host cell to an invading pathogen is crucial to determining the outcome of the infection. Here we will study how host cell stress responses can be harnessed to control bacteria that replicate inside human cells and how some bacteria have evolved to block these responses. This may inform new approaches to control bacterial infections using the innate immune response.

Maintenance of male fertility relies on testis stem cells (spermatogonial stem cells or SSCs) that generate sperm. After chemotherapy, SSCs can be damaged and the recovery of fertility dependent on testis regeneration by surviving SSCs. This project aims to understand the mechanisms underlying SSC survival and restoration of fertility after chemotherapy and promises important insight into potential therapies for protecting and restoring fertility of cancer patients.

We aim to develop a first cell-free approach to regenerative medicine to treat and cure cerebral palsy. We will address this using human amnion epithelial cell derived extracellular vesicles containing neuroprotective cargo that target injured oligodendrocyte cells (brain cells).

Pelvic Organ Prolapse is a neglected gynecological disease affecting 25% of women. There is no cure. Surgical treatments often fail, and the use of vaginal mesh is banned due to unacceptable side effects. This project applies principles nanotechnology to combat such undesirable adversities. Using our unique preclinical models, we will pave the way for new solutions to radically transform health outcomes, reduce healthcare costs and improve women’s quality of life.

Inflammation is central to many diseases, driven by inflammasomes like NLRP3. Overactive inflammasomes contribute to infections, inflammatory diseases, and cancer. However, research often focuses on mice and specific immune cells, overlooking other inflammasomes like NLRP1. This study uses novel drugs, patient samples, and a humanised NLRP1 mouse model to uncover NLRP1’s role in lung and gut diseases, aiming to develop more effective treatments for inflammation, beyond NLRP3 targeting.

Despite remarkable successes in other cancers, immunotherapy of colorectal cancer (CRCs) is not effective in most cases. This is due to the limited knowledge of the target antigens expressed by these tumours and that may favour their recognition and elimination by the immune system of the patient. This project aims at identifying novel classes of antigens that can be exploited to develop innovative mRNA therapeutic vaccines to improve the clinical control of the majority of CRCs.

This project will investigate how mitochondrial cell death is triggered in innate immune cells to microbial threats and the downstream molecular and cellular events that control the immune response. This project is expected to generate new knowledge surrounding how mitochondria respond to environmental threats using advanced genetic, molecular and cell biology approaches. Expected outcomes include an enhanced understanding of cell death signalling networks, advances in cell biology research methods and new interdisciplinary collaborations. This should provide significant benefits to our basic understanding of how mitochondria shape immune responses and identify ways to manipulate cell death for future research and commercial applications.

This project aims to explore cause-and-effect relationships between molecular regulators and age- and sexspecific traits in skeletal muscle loss. Females live longer and are more susceptible to the functional and metabolic consequences of muscle ageing. Yet, our knowledge is overwhelmingly inferred from findings from male cohorts. Our results will establish the role of sex hormones and sex chromosomes on the origins, progression and consequences of age-related muscle loss, identifying transition points when risks to well-being and windows of opportunity are greatest. The project will produce essential knowledge allowing appropriate mitigation of the sex-specific consequences of muscle loss in males and females to promote healthy ageing.