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Characterising the role of PARPs in DNA repair and cancer therapy

The genome of our cells is damaged multiple times each day, by various factors including sunlight and reactive oxygen species. In order for the DNA damage response to be efficient, our cells utilise highly coordinated repair pathways that function accurately and rapidly throughout the damaged cell. Cells that do not repair DNA damage correctly will accumulate damage and display increased genomic instability, which is a key hallmark of cancer cells, promoting their survival and rapid growth. DNA repair pathways are …

Study level
Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Characterise a novel DNA repair protein as a target for cancer therapies

Study level
Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Determining the response to PARP inhibitor treatment of ovarian cancer in mouse xenograft model

Our cellular DNA is constantly under threat from both exogenous and endogenous factors. DNA repair pathways function to maintain genomic stability, preventing deleterious mutations that may ultimately lead to cancer initiation. When a tumour forms, it becomes genetically unstable, allowing environmental adaptation. This genetic instability can also result in gene mutations and protein expression alterations that can be targeted to induce cancer-specific cell death (phenomenon also known as synthetic lethality). For example, it has been shown that cells deficient in …

Study level
Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Light, circadian rhythms and Parkinson’s disease

Up to 98% of patients with Parkinson’s Disease (PD) have non-motor symptoms (Poewe et al. Nature Rev Dis 2017, 3: 17013) and of those, circadian and sleep disorders are the most common (for review, Gros & Videnovic. 2020, Clin Geriatr Med 36: 119). These symptoms become increasingly prevalent during the course of PD and are key determinants affecting quality of life, advancement of overall disability and placement in nursing homes (Shapira et al. Nat Rev Neurosci 2017,18:435). Circadian and sleep …

Study level
PhD
Faculty
Faculty of Health
School
School of Biomedical Sciences

Spatial profiling of the tumour microenvironment

Lung cancers are the leading cause of cancer related deaths in Australia, with a 5-year survival of 15%. With the emerging success of immune checkpoint blockage leading to durable responses and prolonged survival in 15-40% of cases, there is now a need for predictive biomarkers to guide selection for immunotherapies.The immune contexture of the tumour microenvironment (TME) is an important factor in dictating how well a tumour may respond to immune checkpoint therapies (1). Spatial and immunological composition with cellular …

Study level
PhD, Master of Philosophy
Faculty
Faculty of Health
School
School of Biomedical Sciences

Investigating DNA repair mechanisms in aging adult stem cells

When we age the DNA repair systems of our cells become down regulated. This results in reduced DNA repair capacity, enhanced rates of mutation load and may lead to the development of chronic aging-associated diseases including osteoporosis, Alzheimer's and cancer(1). So it is no surprise that genome instability and stem cell exhaustion, which also strongly correlates with the accumulation of DNA damage, are considered hallmarks of aging(2).However, we still lack a clear understanding on how the decrease in DNA repair …

Study level
PhD, Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Developing in vitro 3D models to understand liver disease

Several studies have demonstrated the appropriateness of 3D organoid cultures over the conventional 2D cultures, the advantages of 3D models include replicating the complex attributes of the liver beyond liver-specific metabolism, such as increased cell density, organization, and cell–cell signalling, O2 zonation.In this project we will establish a novel in vitro 3D model to study hepatocyte biology in the context of liver disease. A more comprehensive approach to investigating the intercellular mechanisms of NAFLD will include co-culture of organoids with …

Study level
PhD, Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Testing of novel antibiotic-loaded nanoparticles for treatment of Chlamydia infection

C. trachomatis, sexually transmitted infections of both the female and male human reproductive tract, affects approximately 127 million people globally each year. The major concerning sequela of C. trachomatis infection is infertility in both men and women. This occurs by damaging the upper reproductive tracts, the ovaries and testes most importantly.The majority of research has been focussed on female disease, and male disease has been underestimated and understudied, particularly therapeutics for male infections. Antibiotic therapy is the only therapy currently …

Study level
Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Infection kinetic changes that occur within macrophage-adapted Chlamydia

Chlamydia trachomatis is an obligate intracellular, bacterial pathogen. C. trachomatis infections of the human reproductive tract affect approximately 127 million people globally each year. The major concern of C. trachomatis infections is their ability to cause infertility in both men and women, by damaging the upper reproductive tracts. However, we are still lacking information about how Chlamydia travels around the reproductive tract, and reaches the upper tract (ovaries and testes in particular) to cause this damage.Recent research has shown that …

Study level
Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Understanding the role of the hSSB1 protein in the response to UV induced DNA damage

Melanoma is the 4th most common cancer in Australia. The link between skin cancer and UV exposure is now well established. If a DNA damage induced by UV exposure is left unrepaired, the mutation generated in the genome can lead to cell death or cancer. It is thus highly important to understand of how a cell can repair DNA damage. The main pathway to repair UV DNA damaged is the nucleotide excision repair pathway (NER) (Kamileri I. et al, Trends …

Study level
Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Investigation of genetic factors that contribute to concussion and its outcomes

The health outcomes from traumatic brain injuries (TBIs) and concussion depend on the nature of the injury, but response also varies greatly between individuals, suggesting that genetic factors may play a role. In particular, due to effects of head trauma on balances of ions, neurotransmitters and energy use in the brain, there is suggestion that variation in the genes that encode proteins involved in these pathways, e.g. ion channels, may affect the risk of, as well as response to a …

Study level
PhD, Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Renewal and differentiation in human neural stem cells and their application to understanding neurological disorders

The effective regeneration of brain tissue requires an understanding of the factors mediating the damage as well as the integration of new/replacement cells to form new functional neural networks. The isolation and expansion of human stem cells and limited neural lineage differentiation have provided the foundation for strategies in the treatment of neurodegenerative disorders. We utilise iPSC-derived NPCs and patient-derived (Alzheimer’s disease; AD) iPSCs and neural lineage differentiation of hMSCs, iPSC NPCs and AD iPSCs in neuronal and glial culture …

Study level
PhD, Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

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