Faculty of Health 3

Doctor of Philosophy

ABEYSINGHE, Abeysinghe Arachchillage Pevindu Hasanka

Thesis Title

Exosomes Derived from Dairy Cows for Diagnostics

Supervisors

• Associate Professor Leila Cuttle  (Associate Supervisor)
• Professor Murray David Mitchell  (Principal Supervisor)

Citation

The PhD project concludes that the small extracellular vesicles (sEV) (diameter ~30-200nm) micro-RNA (miRNA) biomarker signatures alter cellular processes and/or pathways and can be utilized as potential diagnostic tools of dairy cow reproductive performance or be developed into therapeutic interventions. The project optimized blood plasma sEV miRNA isolation to identify 14 differentially expressed (DE) sEV miRNAs (FDR < 0.05) between high- and low-fertile dairy cow plasma. Further, miR-181b-5p was validated as a prognostic sEV miRNA biomarker of infertility. Moreover, the project identified sEV from high fertile dairy cow plasma downregulates inflammatory prostaglandin synthases, which may possibly favor the pregnancy status.

BHANDARI, Murari

Thesis Title

Genomic and Virulence Studies of Vibrio cholerae O1 and Non-O1, Non-O139 in Queensland Australia

Supervisors

• Adjunct Professor Flavia Huygens  (Principal Supervisor)
• Dr Amy Victoria Jennison  (External Supervisor)
• Dr Johanna Joy Kenyon  (Associate Supervisor)
• Dr Irani Udeshika Rathnayake  (External Supervisor)

Citation

Australia has its own V. cholerae strains, both toxigenic and non-toxigenic, that are associated with diarrheal illness and extraintestinal infections. This study has elucidated the genotypic features of historic and a recent surveillance environmental V. cholerae strains from Queensland and their phenotypic antimicrobial resistance ability to tested antimicrobials. Furthermore, this study aimed to place genetic context among V. cholerae strains from Australia with international strains. Ongoing monitoring and genomic characterisation of V. cholerae strains from the environment is important and would assist public health departments to track the source of cholera infection early and implement prevention strategies for future outbreaks.

BROWN, Rachel Helena Loraine

Thesis Title

Investigating the Role of Novel Transcripts from the MYCN Locus Driving Neuroendocrine Prostate Cancer

Supervisors

• Dr Brett Hollier  (Associate Supervisor)
• Professor Colleen Coyne Nelson  (Mentoring Supervisor)
• Dr Nataly Stylianou  (Principal Supervisor)

Citation

This thesis characterises the function of N-myc, a protein that has long been associated with aggressive disease and lethal outcomes across cancer types, as well as two previously uncharacterised proteins encoded from the same gene locus. This thesis investigates both the transcriptional and functional effects resulting from the over-expression of each of these three proteins in the context of treatment-induced neuroendocrine prostate cancer. These studies are the first to describe the individual functions of these three proteins, with implications in driving resistance to standard of care androgen targeted and chemotherapeutic agents that are commonly used to treat prostate cancer patients.

CLAY, Megan Elise Gosnell

Thesis Title

Ecogenomic Insights into the Viral Communities of Corals of the Great Barrier Reef

Supervisors

• Associate Professor Simon Jon McIlroy  (Associate Supervisor)
• Dr Lauren Frances Messer  (External Supervisor)
• Professor Gene Tyson  (Principal Supervisor)

Citation

This thesis explores the identity and roles of eukaryotic viruses and phage in seven Great Barrier Reef corals. It provides a baseline characterisation of the viral community and reveals over 20,000 novel viral genomes, uncovering diverse viral communities and their interactions with microbes. The thesis presents the results of genome-centric bioinformatic analyses which identify core coral viruses, previously unknown relationships of phage with beneficial coral microbes, novel auxiliary metabolic genes, and a comparison of different viral analysis methods. Overall, this research provides vital insights into coral-associated viruses, aiding future research of these threatened organisms with potential environmental and societal impact.

DREW, Peter Edward

Thesis Title

Occupational Violence Against Paramedics: Hostility, Mitigation Practices and the Insight of Practice Theory

Supervisors

• Dr Anthony Scott Devenish  (Associate Supervisor)
• Adjunct Professor Vivienne Carol Tippett  (Principal Supervisor)

Citation

Occupational violence is a significant issue in prehospital healthcare with most paramedics reporting some form of patient or bystander aggression in the context of their work. The study examined the effectiveness of paramedic occupational violence mitigation systems and the associated strategies designed to provide management, support, and moderation. The results of the study suggest paramedic occupational violence is a bilateral, dynamic activity that is subject to the transference of social processes between the paramedic and the patient. The study reveals the effective application of occupational violence mitigation practices in paramedicine are impacted by the unpredictability of the prehospital healthcare setting.

EKWE, Adaeze Precious

Thesis Title

Regulatory T Cell-Directed Therapy for Graft-Versus-Host Disease

Supervisors

• Associate Professor Danica Kaye Hickey  (Associate Supervisor)
• Adjunct Associate Professor Corey Smith  (Associate Supervisor)
• Adjunct Associate Professor Siok-Keen Tey  (Principal Supervisor)

Citation

The use of adoptively-transferred regulatory T cell (Tregs) for the treatment of graft-versus-host disease (GVHD) is limited by lack of clinically-applicable cell manufacturing methods. This study presents a good-manufacturing-practice compliant platform for the isolation, purification, expansion and gene-marking of Tregs, overcoming the current challenges associated with Treg-directed therapy for clinical use. This research provides a platform for future phase 1 clinical trials using gene-marked Tregs that can be tracked in vivo, which represents an important step forward in addressing the clinical and translational need in Treg-directed therapies.

ETEBAR, Fazeleh

Thesis Title

Characterisation of Novel Immune Cell Subsets in the Central Nervous System and its Supporting Tissues

Supervisors

• Dr Samantha Joan Dando  (Principal Supervisor)
• Professor Damien Gerard Harkin  (Associate Supervisor)

Citation

This thesis explores the diversity and adaptation of tissue resident immune cells in the central nervous system (CNS) and its supporting tissues. The study focuses on microglia within different regions of the healthy mouse CNS, revealing significant phenotypic and transcriptional variations. Transcriptomic analysis shows distinct profiles for microglia in various CNS regions, including classical homeostatic and non-homeostatic subtypes. Moreover, the research extends to the pia mater and choroid, uncovering diverse immune cell populations with tissue-specific gene expression profiles in these CNS-supporting tissues. The findings enhance our understanding of CNS immunobiology and its potential implications for immune-mediated neurological and ocular diseases.

FOSTER, Andrew Lewis

Thesis Title

Improving the Management of Fracture-Related Infection through Local Antibiotic Therapy

Supervisors

• Professor Ross William Crawford  (Associate Supervisor)
• Dr Fintan Moriarty  (External Supervisor)
• Professor Michael Andreas Schuetz  (Mentoring Supervisor)
• Adjunct Associate Professor Anjali Tumkur Jaiprakash  (Principal Supervisor)

Citation

The development of fracture-related infection (FRI) is a devastating complication in orthopaedic trauma surgery. Treatment requires multidisciplinary input often involving further surgical procedures and prolonged antibiotic therapy. Original research within this thesis includes the first population-based epidemiological and health economic analysis of FRI performed worldwide. These findings demonstrate enormous upside potential to improving current prevention and treatment methods. One potential method of doing so is through improving the delivery of local antibiotic therapy. A novel antibiotic-loaded hydrogel is investigated within a series of large animal models, which demonstrated superiority in prevention and treatment of FRI over currently available clinical treatments.

JAISANKAR, Durgasri

Thesis Title

Influence of Testing Methods on the Evaluation of Peripheral Ocular Optics and Peripheral Visual Performance

Supervisors

• Professor David Andrew Atchison  (Principal Supervisor)
• Dr Marwan Suheimat  (Associate Supervisor)

Citation

Peripheral (out-to-the-side) vision is important for general mobility and tasks such as driving. This study evaluated appropriateness of testing methods used to measure peripheral optics and visual performance. Peripheral optics measurements depended on the instrument used to measure them. The choice of either head or eye movements to set up peripheral optics measurements was not critical, even when contact lenses were worn. The nature of targets, in terms of size and abrupt or gradual loss of contrast near the edge, affected peripheral detection. To measure peripheral contrast detection accurately in the presence of blur, fine spatial frequency sampling was required.

KAPHLE, Dinesh

Thesis Title

Ciliary Muscle Function and Accommodation in Myopia

Supervisors

• Professor David Andrew Atchison  (Associate Supervisor)
• Katrina Leanne Schmid  (Principal Supervisor)
• Dr Marwan Suheimat  (Associate Supervisor)

Citation

Myopia (short-sightedness) is a progressive condition often associated with near work. This research investigated the accommodation system during treatment with myopia-control multifocal spectacles. Meta-analysis of prior work showed that effectiveness of multifocal spectacles reduces with time, even after the first six months. During accommodation, the anterior ciliary muscle thickens, and its overall length reduces, in both emmetropes and myopes. Myopes have the larger lags of accommodation. Multifocal spectacles initially decrease the lags, but over-time the lags increase, and upgrading addition power by 0.50D restores the initial effect. Modifications to add power can sustain the treatment effect for longer periods.

O'CALLAGHAN, Jessica Louise

Thesis Title

Identifying Changes to Placental Gene Expression in Pregnancies with a Small for Gestational Age Infant

Supervisors

• Dr Vicki Clifton  (External Supervisor)
• Dr Adam Ewing  (External Supervisor)
• Yvette Miller  (Associate Supervisor)
• Dr Elise Pelzer  (Principal Supervisor)
• Professor Peter James Prentis  (Associate Supervisor)

Citation

Small-for-gestational-age infants are born full-term, weighing less than a healthy fetal weight. Due to this, these babies have a life-long increased risk of developing health issues. Understanding how these babies grow and develop in utero allows us to identify these infants earlier and potentially develop treatments. This thesis examined the human placenta, the organ responsible for fetal growth during pregnancy, to understand the contribution of this organ to fetal size. Specifically, this work explored the genetic profile of the placenta from pregnancies where the infant was small and identified key pathways that are dysregulated in placental-mediated reduced infant growth.

RAKSHIT, Archayeeta

Thesis Title

Functional  Capability and Higher Order Executive Function in Adults with Amblyopia and Strabismus

Supervisors

• Professor David Andrew Atchison  (Associate Supervisor)
• Dr Debasmita Majhi  (External Supervisor)
• Katrina Leanne Schmid  (Principal Supervisor)
• Adjunct Associate Professor Ann Louise Webber  (Associate Supervisor)

Citation

Amblyopia, is a visual condition characterized by reduced vision, primarily in one eye, and poor depth perception due to abnormal visual development. This research demonstrated that adults with amblyopia and strabismus have poorer functional performance, including for tasks involving fine motor skills, reading, and peripheral visual attention, even when both eyes are used together. These findings indicating that these deficits are not solely due to decreased vision but rather result from abnormal development of higher brain functions related to visual processing.

RASHEDUZZAMAN, Mohammad

Thesis Title

Profiling Glycosylation Changes as a Biomarker in Head and Neck Cancers

Supervisors

• Riccardo Dolcetti  (External Supervisor)
• Newell Johnson  (External Supervisor)
• Dr Lizbeth Moira Kenny  (External Supervisor)
• Daniel Kolarich  (External Supervisor)
• Adjunct Professor Chamindie Kusalini Punyadeera  (Principal Supervisor)
• Dr Xi Zhang  (Associate Supervisor)

Citation

Alterations in protein glycosylation profiles are frequent pathological findings in a number of systemic disorders, including head and neck cancer (HNC). This thesis revealed the first systematic mapping of specific glycosylation features in HNC cell lines as well as tumour tissue. This study identified sialic acid containing glycans (sialylation) are abundant in HNC. Furthermore, inhibition of sialylation significantly interrupted the migration of HNC cells without affecting their proliferation, indicating a vital role of sialylation in HNC cell migration. This study paved the way for further studies aimed at establishing the possible glycome biomarker for diagnostic relevance.

REILLY, Joshua James Kenneth

Thesis Title

A Little Less Heavy, or a Little Less Hated? Exploring the Consequences of a Neuroinflammation Model of Obesity

Supervisors

• Dr Fatemeh Chehrehasa  (Associate Supervisor)
• Dr Kate Emily Matthews  (External Supervisor)
• Dr Hayley Ruscoe Moody  (Principal Supervisor)

Citation

Neuroscientists have historically examined obesity through the lens of food addiction.  This thesis instead explored how a neuroinflammation lens of obesity development may influence both the treatments available for, and stigma experienced by, fat people. The findings demonstrate a relative lack of crisis metaphors and moralising language in neuroinflammation models of obesity.  Additionally, the common neuroinflammation biomarker, translocator protein of 18 kDa, was found to be a promising therapeutic target for diet-induced obesity.

SHAJIB, Md Shafiullah

Thesis Title

Cryopreservation and Utility of Cancer Organoids and Cartilage Microtissues

Supervisors

• Professor Ross William Crawford  (Associate Supervisor)
• Adjunct Associate Professor Michael Robert Doran  (Principal Supervisor)
• Professor Travis Klein  (Associate Supervisor)

Citation

Microtissues, sometimes referred to as organoids or tumour-spheroids, are increasingly common cell culture tools. They can be used as tissue models for drug testing or as building blocks to create larger, more complex tissues. Reproducibility could be improved, and costs reduced, if it were possible to manufacture microtissues at centralised facilities, and then ship this standardised product to laboratories for testing or clinics for use in therapies. The protocols and data described in this thesis offer important insights into how microtissues could be transformed into standardised cryopreserved products.

TASNIM, Sana

Thesis Title

The Relationship Between Migraine and Thyroid Dysfunction

Supervisors

• Professor Divya Deepak Mehta  (Associate Supervisor)
• Professor Dale Robert Nyholt  (Principal Supervisor)

Citation

Migraine and thyroid dysfunction, particularly hypothyroidism, are among the most common disabling diseases. They affect a significant proportion of the population globally, and their prevalence is more common among females as compared to males. Observational epidemiological and case-control studies have suggested a comorbid relationship between them. This PhD project improves our understanding of the relationship between migraine/headache and thyroid traits (hypothyroidism, hyperthyroidism, secondary hypothyroidism, TSH, and fT4). Utilising statistical genetic approaches, I confirm a comorbid relationship between migraine and thyroid traits, as well as headache and thyroid traits. Causal analysis also suggests a potential causal relationship between the traits.

TRAN, Kim Ngan

Thesis Title

Characterizing the Genetic Architecture of Chronic Kidney Disease

Supervisors

• Distinguished Professor Lynette Robyn Griffiths  (Associate Supervisor)
• Associate Professor Rodney Arthur Lea  (Principal Supervisor)

Citation

This thesis explores the genetic factors behind Chronic Kidney Disease (CKD). CKD is a complex condition involving a gradual decline in kidney function. While previous research has identified some genetic links to CKD, many remain undiscovered. The study uses innovative techniques and data from the isolated Norfolk Island population and the UK Biobank to uncover these genetic connections. It delves into rare genetic variants, ancestral influences, and the value of examining multiple disease-related traits simultaneously. The findings enhance our understanding of CKD genetics and may lead to improved early detection and treatment options for this debilitating condition.

VENUGOPAL, Dinesh

Thesis Title

Development of a Low Luminance Vision-Related Performance-Based Measure

Supervisors

• Professor Sharon Bentley  (Principal Supervisor)
• Alexander Andrew Black  (Associate Supervisor)
• Professor Joanne Mary Wood  (Associate Supervisor)

Citation

Many individuals with vision impairment report difficulties with everyday activities performed under low luminance conditions. This research involved the development of a new comprehensive vision-related low luminance performance-based measure, the 'Assessment of Low Luminance Vision-Related Activities (ALLVA)'. The ALLVA was shown to be a valid and reliable instrument. The ALLVA could be used to better understand and quantify difficulties in performing vision-related activities under low luminance conditions, and evaluate low luminance injury prevention programs, the effectiveness of eye therapies and the outcomes of low vision rehabilitation in people with vision impairment.

VITHARANAGE, Achala Shenali Fernando

Thesis Title

Identification and functional characterisation of IRX4 isoforms in prostate cancer

Supervisors

• Professor Jyotsna Batra  (Principal Supervisor)
• Dr Panchadsaram Janaththani  (External Supervisor)
• Dr Indira Prasadam  (Associate Supervisor)

Citation

The Iroquois (IRX) transcription factors belong to the homeobox protein family and have vital physiological functions in humans. Recent studies show that they are linked to human cancers, particularly Iroquois-class homeodomain protein 4 (IRX4) has been implicated in prostate cancer. In this thesis, four protein isoforms derived from alternative splicing of IRX4 were discovered in prostate cancer patients. They were found to have differential roles and mechanisms of action in prostate cancer pathogenesis. Additionally, the expression levels of identified IRX4 isoforms were evaluated in prostate cancer patient samples for their potential diagnostic and prognostic significance.

YARLAGADDA, Tejasri

Thesis Title

The Interactions between Probiotic Bacteria and Respiratory Viruses within the Epithelium of the Upper Respiratory Tract

Supervisors

• Dr Alison Jane Carey  (Associate Supervisor)
• Anders Cervin  (External Supervisor)
• Adjunct Professor Flavia Huygens  (Associate Supervisor)
• Professor Kirsten Michelle Spann  (Principal Supervisor)

Citation

This thesis investigated the interactions between probiotic bacteria and respiratory viruses within the epithelium of the upper respiratory tract. Utilizing a novel 3D culture method, to mimic a real-life nasal epithelium, it was demonstrated that probiotics dampen viral-induced inflammation of the nose. The findings provide a unique insight into the beneficial role of probiotic bacteria during viral infection of the upper respiratory tract.