Higher Degree by Research

Chief Investigator

Project title

Project description

Preferred educational background

Dr Snehlata Kumari

s.kumari@uq.edu.au

Deciphering immune regulatory mechanisms of skin inflammation

The skin forms immunological, mechanical and structural barrier to protect the organisms from external challenges. Active communication between soluble factors and cells in skin, such as epithelia, stromal and immune cells are crucial to maintain skin homeostasis. Recent studies have highlighted consequences of perturbed communication in the development of inflammatory skin diseases.

This project aims to understand and identify immuno-modulatory factors and mechanisms regulating skin inflammation to help develop new therapeutic strategies for inflammatory skin diseases.

The project provides excellent opportunity to PhD candidates to learn and engage in techniques in Immunology, Molecular Biology, Cell Biology and Genetics including CRISPR/Cas9-mediated genetic engineering, flow cytometry, microscopy and in vivo models.

BSc (Hons) or MSc in biological or biomedical science.

Professor Gabrielle Belz

Our work aims to understand how the immune system responds to (infections (including viruses, bacteria and parasites) and tumour cells. We are investigating how different types of immune cells develop, and what factors influences their decision to become one type of immune cell or another to mediate long term immune protection. Understanding how the body deals with pathogens will give clues about how to enhance protective immunity. Our goal is to discover new therapies that boost our immune system to protect against infection. We aim to: · Identify novel functions of innate lymphoid cells and NK cells in immune protection · Unravel the microbome-epithelial-immune interface protecting mucosal surfaces · Elucidate the mechanisms responsible for the generation of protective immunity in response to lung and gastrointestinal pathogens Combining cellular, molecular biology, and high throughput technologies the candidate will investigate the role of novel transcription factors in governing innate cell fate using a number of approaches including flow cytometry, imaging and molecular approaches.

Immunity and Inflammation, Cancer

Professor David Evans

d.evans1@uq.edu.au

Investigating the relationship between left-handedness, disease and other life outcomes

Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we recently conducted the world’s largest genetic study of handedness in over 1.7 million individuals (Cuellar-Partida et al 2020). We found 41 genetic loci associated with left-handedness and 7 associated with ambidexterity (P < 5 × 10−8). We would now like a student to take this work forward and use this resource to investigate the relationship between handedness and a variety of life outcomes including mortality and disease. The successful candidate will gain experience across a wide range of advanced statistical genetics methodologies including Mendelian randomization (a way of using genetic variants to investigate putatively causal relationships), genome-wide association analysis (GWAS), genetic restricted maximum likelihood (G-REML) analysis of genome-wide data which can be used to partition variation in phenotypes into genetic and environmental sources of variation, and instrumental variables analysis (using natural “experiments” to obtain information on causality from observational data).

Epidemiology, Statistics, Genetics, Psychology

*The successful candidate must commence by Research Quarter 4, 2021. You should apply at least 3 months prior to the research quarter commencement date. International applicants may need to apply much earlier for visa reasons.

Professor Di Yu

di.yu@uq.edu.au

Differentiation and function of novel cytotoxic T-cell subsets

Cytotoxic CD8+ T (Tc) cells constitute the major immune cell type that is responsible for eliminating infected or cancerous cells. Tc cells differentiate into specialised subsets that localise to specific tissues and organs to perform their cell killing functions but may also mediate immunopathology. Professor Di Yu's laboratory poineers in discovering new T cell subsets and unveiling mechanisms underlying their differentiation and function. This project will utilise both pre-clinical animal models and bioinformatic approaches to characterise novel Tc subsets, including ‘follicular cytotoxic T cells’ (Tfc cells). The gained new knowledge will help to design new strategies to treat cancers and infectious diseases such as caused by HIV, EBV and SARS-CoV-2.

• A working knowledge of Immunology, Cell Biology and Bioinformatics would be of benefit to someone working on this project.
• Applications will be judged on a competitive basis taking into account the applicant’s previous academic record, publication record, honours and awards, and employment history.
• The applicant will demonstrate academic achievement in the field(s) of biomedical sciences and the potential for scholastic success.

*The successful candidate must commence by Research Quarter 1, 2021. You should apply at least 3 months prior to the research quarter commencement date. International applicants may need to apply much earlier for visa reasons.

Dr John Kemp

j.kemp2@uq.edu.au

Identifying pharmacological targets for osteoporosis intervention using whole-genome and exome sequencing of bone related phenotypes

Osteoporosis (OP) is an often asymptomatic multi-factorial condition that is characterized by a progressive loss of bone mass resulting in increased fracture (FX) risk and reduced lifespan(1). It represents a significant public health burden that affects an estimated 2.2 million Australians and results in 20,000 hip fractures annually, with direct and indirect disease-related costs estimated at $7.4 billion per year(2). Due to the insidious nature of this disease, individuals who are most at risk of OP are often only identified once they present with low trauma FX. The situation is further exacerbated as most pharmacological treatments function as anti-resorptives that halt further bone loss, but fail to fully restore bone quality. Only one osteoanabolic drug is presently approved by the United States Food and Drug Administration, however this compound is far from ideal as it requires daily administration via injection to ensure adequate bone formation(3). Consequently, there is considerable scope for identifying novel osteoanabolic pathways that could in principle be targeted by new and existing pharmacotherapies to build bone mass before clinical sequelae develop.

The goal of this PhD is to combine statistical and molecular genetics approaches to identify and assess the therapeutic potential of OP drug targets.

AI & Machine Learning, Bioinformatics, Computer Science & IT, Endocrinology, Genetics, Information Science, Molecular Biology, Public Health & Epidemiology, Software, Engineering, Statistics

*The successful candidate must commence by Research Quarter 4, 2022. You should apply at least 3 months prior to the research quarter commencement date. International applicants may need to apply much earlier for visa reasons.

Dr Mathew Jones

mathew.jones@uq.edu.au

Targeting DNA replication and repair in human cancer cells

DNA replication is the fundamental mechanism of genetic inheritance and an essential process for all cellular life. In cancer cells, replication is corrupted and replication forks frequently stall and collapse causing DNA damage and copying errors that drive tumorigenesis. As a result, cancer cells are heavily dependent on the pathways that protect and repair stalled replication forks. Disrupting these mechanisms can be selectively toxic to cancer cells. A key player in the regulation of DNA replication and repair is DDK (Dbf4-dependent kinase also known as Cdc7). DDK is frequently overexpressed in cancer, but its role during DNA replication and the repair of stalled replication forks has not been well characterised. Our research uses chemical genetic approaches to selectively target DDK and gain valuable insights into its requirements and molecular targets. This project aims to understand how DDK coordinates DNA replication and repair to help develop new therapeutic strategies to target these processes in cancer cells. This project is suitable for a PhD student and provides an excellent opportunity to learn molecular and cell biology techniques and gain experience with long-read genome sequencing tools and genome engineering methods (CRISPR/Cas9).

Genomic Medicine, Cancer

This project is suitable for PhD students.

BSc Hons or MSc in biological or biomedical science

Associate Professor Emma Hamilton Williams

e.hamiltonwilliams@uq.edu.au

Islet specific T cell responses in type 1 diabetes

Type 1 diabetes (T1D) is the most common chronic disease of childhood. It is triggered by an immune dysregulation causing T cells to attack the insulin-producing islet beta cells in the pancreas. This results in elevated blood-glucose and severe life-long complications. Our laboratory aims to develop a T cell targeted immunotherapy to prevent or treat T1D. For this goal to be successful, better tools are needed to detect and characterise islet-specific T cells in patient blood as a way to monitor responses to immunotherapy. An understanding is needed of how these T cell responses vary between different patient groups. This project aims to develop an approach to personalised immunomonitoring of islet specific T cells using state-of-the-art high-parameter immune profiling, single cell sequencing and clonotype analysis of islet-specific T cells in patient blood. This approach will later be used to characterise how these T cells respond to immunotherapy. The ideal candidate will have prior knowledge and academic achievement in the field of immunology. Practical experience in T cell biology, autoimmunity or sequencing analysis would be desirable. This project is aligned with a National Health and Medical Research Council funded grant and will be co-supervised by A/Prof Emma Hamilton-Williams, Prof Ranjeny Thomas and Dr Mark Harris. The supervisor team are highly experienced and provide broad expertise and experience in immunology, translational and clinical research.

Immunity and Inflammation, Immunotherapy

This project is suitable for PhD students

BSc Hons or MSc in biological or biomedical science

Associate Professor Fiona Simpson

f.simpson@uq.edu.au

Cancer therapy endocytosis

This is a project which aims to investigate how tumours and normal tissue internalise drugs such as cancer therapy antibodies in real in vivo models and in patients. My laboratory has recently shown that changing this internalisation can alter therapy mechansims. The uptake of drugs by both target cells and normal cells in humans, a process called endocytosis, is critical for many medicines including antibody therapies, nano-medicines and antibody-drug conjugates (ADCs). Our understanding of cellular uptake mechanisms has developed significantly in the last 5 years. However, these advances in cell biology have not fully translated to the drug delivery, design and immunological fields. The role of endocytosis is also important for naturally occurring nanoparticles, such as viruses and exosomes and CAR-T therapy has been shown to be antigen clustering dependent. An example of this is the recent advance in cancer therapy using anti-PDL1 and anti PD-1 antibodies, known as checkpoint inhibitors. Recent data has shown that in cases of poor outcome the pharmacokinetic properties of anti-PDL1 antibody is an issue, with tumour degradation of the antibody occurring very quickly. Another example is the drive to understand CoV-virus entry into human cells to inform to inform potential anti-viral therapies. Findings from our program may be applied to multiple clinical settings (e.g. antibody therapy in multiple sclerosis or anti-HIV antibody therapy). This project crosses the fields of cell biology, immunology, cancer, drug targeting and clinical trials. Techniques include (but are not limited to) imaging, electron microscopy, fluorescence activated cell sorting and in vivo work in murine models and patient samples.

Immunotherapy, Cancer, Skin and Skin Cancer

This project is suitable for PhD students.

BSc Hons or MSc in biological or biomedical science

Dr Aideen McInerney Leo

We are focused on increasing genomic literacy and genomic confidence in both patients and non-genetics clinicians to democratize access to genetic testing. This includes developing educational videos, interactive websites and chatbots for consumers. For clinicians we are exploring the impact of different, evidence-informed educational interventions. Our latest research projects evaluate how best to return polygenic risk scores to individuals, optimize educational materials, train clinicians and evaluate the psychological and behavioural impact of these results. In genetic tests associated with minimal, if any psychological distress (e.g. genetic testing for melanoma) we are randomizing consumers to receive genetic testing from a trained non-genetics clinician or genetic counsellor to determine whether psycho-behavioural outcomes differ with provider type. Results from our research have the potential to inform practice guidelines and accelerate the integration of genomics into clinical care.

Skin and Skin Cancer, Genomic Medicine

Professor Brandon Wainwright 

Brain cancer is the most common cause of cancer-related death in children. The Wainwright laboratory discovered the first gene known to cause brain tumours in children and since that time has been focused on using genetic/genomic and developmental biology approaches to understand the genesis of paediatric brain tumours and develop new therapies. The Children's Brain Cancer Initiative based at UQDI is a collaboration between multiple Universities and Research Institutes, and the Queensland Children's Hospital. As part of this Initiative we have PhD scholarships for suitably qualified applicants.

Cancer, Genomic Medicine, Immunotherapy

This project is suitable for PhD students.

Professor Mark Morrison

This PhD project aims to provide a deep functional understanding of recently discovered microbes from the Domain Archaea that inhabit the digestive tracts of native Australian herbivores, humans, and other animals. In consultation with the supervisory team, the successful applicant will develop a research plan that brings novel Archaeal taxa to life via metagenomics. The person will also use our globally unique collection of bioresources and innovations in molecular microbiology research, to help define the roles of Archaea in the low methane carbon economy of native Australian herbivores. Very little is known about the genetics and biology of methanogen x host specificity in all these animals. This project will help address the knowledge gaps and support the development of new strategies relevant to the health, population dispersal, and conservation of these iconic animal species. The knowledge gains from this project are also expected to provide new opportunities relevant to medicine and agriculture. As such, the project's national benefits are both timely and broad, and should be of interest to applicants with interests in natural sciences, medicine, or agriculture.

None Of The Above

Dr Arutha Kulasinghe

This project aims to understand the underlying tumour microenvironment in lung cancer to identify cellular locations, phenotypes and activation status that may associate with response to immunotherapy. The project will use cutting edge technologies to cellularly map lung cancers.

Cancer, Immunotherapy

Professor Michael Stowasser

This is a PhD opportunity to work with a team of clinician-scientists on clinical and laboratory research elucidating the role of the mineralocorticoid hormone receptor in cardiometabolic health/inflammation, and optimising diagnostic approaches for, and elucidating the pathogenesis of, primary aldosteronism at the world-renowned Endocrine Hypertension Research Centre, UQDI based at TRI and Princess Alexandra Hospital. The successful candidate will be considered for scholarship and top-up support.

None Of The Above