MBI PhD Students

We include profiles of some PhD students currently working with MBI affiliated supervisors. Projects cover the whole spectrum from basic science discovery, clinical medicine, epidemiology and public health to service delivery and implementation research. Prospective students are welcome to contact MBI at mbi@sydney.edu.au for linkage to potential supervisors, or to make direct contact with any specific supervisors identified.

Cristina Sotomayor - Salmonella related cases among the serovars enteritidis and typhimurium

Cristina Sotomayor

I’m a year 1 Ph D student from Chile, learning and doing research on the food-borne diseases area, particularly on Salmonella, at the Centre for Infectious Diseases and Microbiology, ICPMR, located in Westmead Public Hospital. I have a MSc in Public Health and Epidemiology from UACh, Valdivia, Chile.
Diseases caused by the consumption of contaminated food, have emerged as an important cause of morbidity and mortality worldwide. Some countries, including Chile and Australia, have experienced an increased presentation of salmonella related cases lately, particularly among the serovars enteritidis and typhimurium. This last one, is a particularly epidemic serotype with a ubiquitous host range that is commonly responsible for clinical disease in both livestock and humans. It is the most common isolated serovar found in NSW (over 50% from 2001 till now), linked to specific changes involving food production chain; its persistence in time is ensured by the overall lack of effective control and prevention measures. Molecular typing methods such as MLST and MLVA have been used for further discrimination of Salmonella serovars; this has allowed the identification of particularly successful clones among NSW territory for the last 5 years period, optimizing and strengthening the current epidemiological surveillance protocols through the recognition of these circulating clones. Further analysis, including whole genome sequencing will add powerful information to the current situation of salmonellosis in NSW and Chile. The general aims of my current research is (1) to analize traditional and molecular epidemiology present in community outbreaks from Chile and NSW caused by Salmonella serovar typhimurium, (2) to compare temporo-spatial patterns in these community outbreaks as an active surveillance tool.

Cristina is supervised by A/Prof Vitali Sintchenko

Sophie Lev - signaling pathways essential for the development and virulence of C. neoformans

Sophie Lev

I completed my PhD in the Technion - Israel Institute of Technology, followed by post-doctoral training in the same University, and then in the University of California, Berkeley. I joined the Fungal Pathogenesis lab in Westmead as a research fellow in 2010.

Cryptococcus neoformans is an opportunistic human fungal pathogen that presents a significant threat to immunocompromised people. My research focuses on the signaling pathways essential for the development and virulence of C. neoformans. Specifically. I am studying the role of differentially phosphorylated inositol molecules (inositol polyphosphates) in gene expression, chromatin remodeling, phosphate storage, protein secretion and, ultimately, the virulence of C. neoformans. The long-term purpose of this work is to identify specific inhibitors of the inositol polyphosphate biosynthesis pathway which would have the potential to become novel antifungal drugs.

Sophie is supervised by Dr Julianne Djordevic

Dr Hal Willaby - Investigating the psychological and social factors related to vaccine uptake

Hal Willaby

Dr. Hal Willaby is a Research Fellow in the School of Public Health at the University of Sydney, with a conjoint appointment to the National Centre for Immunisation Research and Surveillance (NCIRS). His work investigates the psychological and social factors related to vaccine uptake. In particular, Hal is interested in determining the belief and attitude structures associated with risk perceptions of vaccine-hesitant parents, and validating a measure of those structures that can be used to inform targeted interventions. Hal is also contributing to the development and trial of the Vaccine Communication Framework – a resource for primary healthcare providers to address the concerns of vaccine-hesitant and vaccine-refusing parents.

Hal is supervised by Julie Leask

Valery Combes - Role of microparticles and their composition in the pathogenesis of cerebral malaria

Valery Combes

Dr Valéry Combes is a vascular biologist and works on a particular aspect of cell biology: the shedding of microparticles (MP). She obtained her PhD in 2001 on the role endothelial MP in the pathogenesis of thrombotic diseases at the Université de la Méditerranée (Marseille, France). From 2006 to 2012, she was a Research Fellow in the team of Prof Grau at the University of Sydney after a post-doctoral fellowship in France and is since then a Senior Research Associate, leading, in this team, the work on the vesiculation of endothelial cells. During her post-doctoral research, she has been involved in the field of malaria and more specifically in the pathogenesis of cerebral malaria, in an experimental murine model, in vitro approaches and clinical studies. Since her appointment at the University she has broaden her interest in the field of microparticle biology to other infectious diseases such as tuberculosis and sepsis.

Valery is supervised by Professor Georges Grau

Julie Wheway - Dysregulation of the immune system in cerebral malaria

Julie Wheway

Dr Julie Wheway is a postdoctoral fellow in the Vascular Immunology Unit. Currently, her research focuses on the dysregulation of the immune system in cerebral malaria (CM), specifically how the brain endothelium modulates T cell responses during infection. Her research examines the immunomodulatory and antigen presenting capacity of endothelial cells, the cells that form the inner lining of blood vessels. Particularly, whether endothelial cells are able to present antigens to T cells during CM infection. This research has uncovered a novel role for the endothelium in supporting T cell proliferation and antigen presentation. More recently Julie’s research has focused on how endothelial microparticles (EMP) interact with and modulate immune cells. Understanding effector functions of EMP may shed light on disease pathogenesis of CM, but also immune-inflammatory diseases such as atherosclerosis, sepsis and multiple sclerosis which all have high plasma levels of EMP.

Julie is supervised by Professor Georges Grau

Ulziijargal Gurjav - Multi-drug resistant M.tuberculosis strains in Mongolia: Exploring differences between typical and atypical Beijing strains

Ulziijargal Gurjav

I'm a second year PhD student at the Centre for Infectious Diseases and Microbiology, ICPMR. And I have Master of Science degree from the University of Hawai'i at Manoa, USA.

Worldwide emerging M.tuberculosis Beijing family’s epidemiology, disease progression and drug resistance are well documented. However continuous transmission of Beijing family is posing major public health threat in tuberculosis (TB) low and high incidence countries. Therefore detailed molecular epidemiological study is needed in both areas. Also it has been shown that due to homoplasy of M.tuberculosis genome, current standard fingerprinting using MIRU-VNTR region is less discriminatory especially for Beijing genotype. Thus high resolution typing is essential for TB control and surveillance. Therefore my doctoral research project aims 1. to investigate distribution and changes of Beijing and East-African-Indian lineages of M.tuberculosis overtime in NSW, Australia and Mongolia, 2. to design and evaluate new rapid SNP based typing method to characterize and classify Beijing and EAI strain clusters. Since 1986, Australia maintained low TB incidence, 5-6 cases per 100000 population per year as compared to Mongolia, TB high-incidence country, had 223 TB incidence cases per 100000 population in 2011. Thus comparative epidemiological study of NSW, Australia and Mongolia will help determine dynamics of lineage composition over time, rate of recent transmission, cluster rate, number of clusters and association of lineage with high risk population which will eventually contribute to tailored public health measures in TB low and high transmission areas.

Ulzi is supervised by Dr Vitali Sintchenko

Qi Zhou - Inhalation therapy of antibiotics for respiratory infections

Qi Zhou

Dr Qi (Tony) Zhou is an NHMRC Early Career Fellow in the Faculty of Pharmacy, The University of Sydney. Dr Zhou’s research focuses on inhaled powder formulation of antibiotics for treatment of respiratory tract infections. Respiratory tract infections are expected to be one of the major priorities for the Australian healthcare system including the acute infections of pneumonia and the chronic cystic fibrosis. However, traditional oral or intravenous administrations of antibiotics may have difficulty to deliver drug to the infected site in respiratory tracts. In contrast, inhaled aerosols of antibiotics can be delivered directly to the respiratory tracts. Dry powder inhalers are among the most promising ways to provide a safer, cheaper and more efficacious solution for the treatment of respiratory infections.

Zhou (Tony) is supervised by Professor Kim Chan

Thaigarajan Parumasivam

Thaigarajan Parumasivam

Tuberculosis (TB) a highly infectious disease caused by Mycobacterium tuberculosis, is a leading cause of illness and death globally. The current chemotherapy of TB is based on oral route administration of at least three first-line drugs in combination with direct observation on patient compliance. However, in the last decade, the number of drug resistant cases had been increasing at an alarming rate which makes the competence of DOTS strategy questionable. Studies have coined out that one of the reasons for the emergence of drug-resistant strains in TB patients is the exposure of tubercle bacilli to a sub-therapeutic levels of one or more drugs. Studies also emphasized that the conventional therapy especially by the oral routes may lead to sub-therapeutic levels of anti-TB agents owing to poor pulmonary distribution of these systemically administered drugs. Thus, anti-TB drug delivery via the pulmonary route provides rationale strategies to circumvent this problem as the lung is the primary portal of tubercle cells entry that cause pulmonary tuberculosis.
Our research aimed to evaluate the potential of delivering vaccine and a drug combination therapy, containing first-line and second-line anti-TB drugs, as a dry powder inhaler formulation for inhalation.

Thaigarajan is supervised by Professor Kim Chan and Professor Warwick Britton

John Chan - Pharmaceutics involving formulation of novel anti-tubercular dry powder aerosols

John Chan

Tuberculosis (TB) remains a debilitating economic, social and medical burden in developing nations worldwide despite a well-established oral treatment regimen. Our research focuses on targeted delivery to the pulmonary site of infection with novel inhaled anti-tubercular treatments. Lung delivery may allow for a reduction in current side effects, drug dosing levels and treatment time (6 months) associated with oral formulations. Our working formulation is an inhaled excipient-free antibiotic dry powder for maximum drug delivery to the lungs. Future formulations will focus on more specific targeting of TB-infected alveolar macrophages.

John has a Bachelor of Pharmacy from USYD. His honours project was on nebulisation of osmotic agents for cystic fibrosis.

John is supervised by Associate Professor Daniela Traini

Kavya Swaminathan - Antivirals against the influenza virus

Kavya Swaminathan

Kavya Swaminathan is a PhD candidate in the Downard Laboratory in the School of Molecular Bioscience. Her research interests focus on studying antivirals against the influenza virus. Influenza outbreaks cause millions of deaths annually and antivirals play a critical role in controlling the virus. Her research involves application of high resolution mass spectrometry based approaches to study the binding of novel and existing inhibitors to the viral antigens. In the light of newly emerging resistant strains the approach is also being extended to characterize drug-resistant mutants of the virus.

Kavya won an outstanding achievement award from the Faculty of Science in 2012.

Kavya is supervised by A/Professor Kevin Downard.

Sharissa Latham - Membrane-cytoskeletal interactions in pro-inflammatory mediated vascular cell vesiculation

Sharissa Latham

Microparticles (MP) are plasma membrane-derived submicron vesicles produced during physiological conditions, upon cellular activation and during apoptosis, in a process termed vesiculation. MP are carriers of biologically active surface, cytoplasmic and nuclear markers donated from their cell of origin, allowing them to regulate and exacerbate physiological processes such as haemostasis, proliferation, coagulation and inflammation. Elevated levels of endothelial derived MP are observed in numerous diseases, including cerebral malaria, sepsis or multiple sclerosis, increasingly supporting roles as a promoter of disease progression. Whilst modifications to phospholipid asymmetry, cytoskeletal-protein organisation and integrity have been implicated in vesiculation, the precise mechanisms of this process are not completely understood.

The project examines the mechanisms of agonist-induced endothelial vesiculation in vitro, in particular investigating the response to various inflammatory and immunopathological stimuli including tumour necrosis factor (TNF), lipopolysaccharide (LPS), interferon-γ (IFN-), and Plasmodium falciparum infected red blood cells (iRBC). The study aims to describe the precise cytoskeleton-membrane interactions required for membrane blebbing to occur, and explores a role for the actin-cytoskeleton in actively facilitating this phenomenon.

Sharissa is supervised by Prof Georges Grau and Dr Valery Combes

Dr Jen Kok - Respiratory Infections in Critical Care Setting

Dr Jen Kok

Dr Jen Kok is an infectious diseases physician, clinical microbiologist and research fellow at the Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR, Westmead Hospital, NSW. His interests include respiratory viruses, in particular influenza; and infections in the critically unwell and immunocompromised hosts. He is currently undertaking postgraduate research in respiratory infections in the critical care setting, focusing on diagnostics, host responses and antimicrobial resistance.

Jen is supervised by Professor Jon Iredell

Karen Williams - Shiga Toxin producing E. coli

Karen Williams with a cow

Cattle are a reservoir of the human pathogen E coli O157 which ‘colonises’ the intestinal tract of the animal and is shed in the faeces. The nature of this shedding is heterogeneous with regards both level and duration of shedding. This variation between animals and more specifically the phenomenon of super-shedding (>10000 cfu/g faeces) is poorly understood with significant public health implications.

This project involves a longitudinal study of cattle to monitor the levels of O157 excreted by cattle over time in the course of natural infection. This will provide a clearer picture of shedding levels and variances. The project will be looking at the patterns from an epidemiological point of view and aiming to identify risk factors that affect the level or duration of shedding.
In vitro studies to assess the nature of bacterial attachment to the bovine gastro-intestinal tract (GIT) will further investigate the nature of differential shedding. The use of primary bovine cells isolated from the GIT will be used as a model for adhesion trials.

Karen is supervised by Professor Michael Ward and is co-supervised by Dr Om Dhungyel and Dr Karren Plain.

Fatima El-Assaad - Pathogenesis of cerebral malaria: Plasmodium, microparticles and miRNA

Fatima El-Assaad

Fatima El-Assaad is a final year PhD student whose research involves understanding the underlying pathogenesis that drives the manifestation of experimental cerebral malaria. Malaria ranks along with HIV and TB as one of the 3 greatest infectious diseases and continues to be a major global health problem, with half of the world’s population at risk. Cerebral malaria is characterized by coma and seizures in the presence of Plasmodium falciparum in the blood. Currently, there is no single treatment that allows for 100 % recovery. Despite better campaigns targeted at the eradication of malaria and the associated syndromes, the global burden still persists. Progress is hampered by emerging antimalarial resistance, problems in vaccine development and lack of health care resources in endemic countries.

Using available in vitro and in vivo models of malaria, her research focuses on the role of circulatory plasma microparticles in the progression of the syndrome, particularly describing their production, phenotype, tissue localisation and their ability to transfer pathology in healthy hosts. She is also testing candidate modulators of microparticle production, as potential therapies of cerebral malaria. Her work studies the potential role of microRNAs, regulators of gene expression and also the cytoadherence of Plasmodium berghei in the development of murine cerebral and non-cerebral malaria.

Fatima El-Assaad is supervised by Prof Georges Grau and Dr Valery Combes

Dr Greg Fox - Environmental and genetic risk factors for tuberculosis

Greg Fox

Dr Greg Fox is an Australian Respiratory Physician, with a Masters of International Public Health. He has lived for over 3 years in Hanoi, Vietnam, where he is undertaking a PhD focusing upon environmental and genetic risk factors for tuberculosis. Greg is co-ordinating a tuberculosis contact investigation study among household members of tuberculosis patients in 8 Provinces throughout the country. His research interests include the clinical and public health strategies to enhance tuberculosis diagnosis, development of evidence-based policy in tuberculosis control and the contribution of host genetic susceptibility to disease burden in high-prevalence settings. He is a member of the Vietnam Stop TB Partnership, and has a strong interest in epidemiology and research training in resource-limited settings.

Greg is supervised by Professor Guy Marks and co-supervised by Professor Warwick Britton

Fadl Bdeir - Disease Outbreak Coordination

Fadl Bdeir

In this research, we aim to explore the patterns of inter-organizational response to disease outbreaks and develop social networks based measures for modelling and evaluating the coordination behaviour.

We argue that coordination behaviour in a highly dynamic context such as responses disease outbreaks represent nonlinear patterns leading to emerging group behaviour. We further apply social networks based theory such as "Structural Holes" and "Strengths of Strong and Weak Tie" theory for explore the effectiveness and efficiency of optimized social network structures for improve response and intervention effort for disaster.

Fadl Bdier is supervised by Professor Liaquat Hossain and co-supervised by Professor John Crawford

Christa Dewi - Reducing Tuberculosis in Eastern Indonesia

Christa Dewi

I work for a local NGO that focuses on providing primary health care, especially in remote areas in Indonesia, such as East Nusa Tenggara, West Nusa Tenggara, as well as Timor Leste.

The topic of my research is 'The contribution of a community-based approach in reducing tuberculosis (TB) in Eastern Indonesia'. We would like to explore the effectiveness of community-based TB program in order to improve the identification, management and treatment of TB through increasing the capacity of the village health volunteers (VHVs).

Many Asian countries have a long experience of community contribution to TB care, but the documented experience in countries in Asia is scanty. Similar work has not been carried out in Indonesia despite the high incidence of TB and an absence of formally qualified health workers at a village level. Many areas such as Flores (the site of the research) is also a geographically difficult area in which to work.

Christa is supervised by Professor Lesley Barclay AO.

Hui Xin Ong - Epithelial Profiling of Controlled Release Antibiotic Respiratory Formulations

Hui Xin Ong

Respiratory tract infection is very common and represents the largest proportion of the antibacterial market. Rapid pulmonary antibiotic absorption and clearance suggest controlled release (CR) inhaled antibiotic formulations would be beneficial for the treatment of chronic infections. However, there is currently no standardised pharmacopoeia method to evaluate the in vitro release rates for respiratory formulations. This could be attributed to the lack of predictability and correlation between available in vitro to in vivo models for pulmonary drugs. Hence, the aim of this project is to develop and validate an airway epithelium model which is capable of monolayer differentiation and mucus production, for its effectiveness in predicting the release kinetics of controlled release antibiotic formulations delivered to the lungs. The formulations currently being investigated include liposomal ciprofloxacin and dry powder ciprofloxacin spray-dried with PVA.

Hui Xin is supervised by A/Prof Paul Young, A/Prof Daniela Traini and A/Prof Mary Bebawy.

Beryl Wen - Monocyte and microparticle membrane transfer to endothelial cells in a model of endotoxic shock

Beryl Wen

Septic shock, an aggressive disease state characterised by the body’s life threatening response to infection, is currently the chief cause of death from infectious diseases in developed countries. In Australia, sepsis occurs in 1-2% of all hospitalisations with mortality rates of up to 30%. Globally 18 million cases of sepsis occur each year despite the major advances in medical research, highlighting the need to unravel the pathogenesis rather than just focusing on the treatment of sepsis.

Complex interactions between endothelial cells and circulating monocytes are responsible for microvasculature dysfunction, especially during sepsis, septic shock, and other blood-brain-barrier pathologies due to Gram-negative bacteria. Microparticles are membrane-derived submicron vesicles that are associated with various diseases including infectious pathologies. However it is unknown whether microparticles derived from activated monocytes may contribute to inflammatory processes and notably vascular leakage.

This study aimed to analyse the physical interactions between endothelial cells and both monocytes and their derived microparticles generated by endotoxin (lipopolysaccharide, LPS).

Beryl is supervised by Prof Georges Grau and Dr Valery Combes