The Human Malaria Immunology Group’s goal is to inform the development of effective malaria vaccines by defining functional mechanisms of antibodies that target the parasite, and the development of protective antibodies in humans.
Currently, the most advanced malaria vaccine has only 36 per cent efficacy, with efficacy further reduced in infants and in populations with high prior malaria exposure. We aim to inform the development of next-generation malaria vaccines by:
- identifying and characterising key functional mechanisms of antibodies that mediate protection,
- defining the key cellular mechanisms that promote the generation of functional antibodies, and
- quantifying the impact of host age and prior malaria exposure on antibody development.
Our research is focused predominately in humans. We leverage human samples from controlled human malaria infection models and human clinical cohorts of malaria infection, and apply these clinical samples to in vitro systems.
We have shown that a large proportion of antibodies that target the blood stage of malaria infection require complement fixation to prevent RBC infection (Boyle et al, Immunity, 2015).
Antibody development requires the correct activation of CD4 T cells during infection. Using a large clinical cohort of children and adults from Uganda, we have shown that the development of malaria-specific CD4 T cells is independently affected by age and prior malaria exposure.
We are currently focused on defining the role of T-follicular helper cell in the induction of functional antibodies against malaria.
Publications
Student Projects
Modification of neurodevelopmental programming with Mediterranean diet and impact on mental health
Immune activation and inflammation during pregnancy plays an important role in the development/severity of major mental illnesses, such as mood disorders, anxiety, depression, behavioural disorders and schizophrenia. Preliminary evidence showed that the cross talk between the microbiome and the immune system plays a major role. We propose to investigate whether a diet with anti-inflammatory properties, such as the Mediterranean diet, implemented during pregnancy and/or in the early stages of life can reduce the onset and severity of mental disorders. We will use an experimental approach to determine the impact on brain connectivity using MRI imaging, Flow cytometry and fluorescence imaging to visualise and characterise the immune responses, and we will use metagenomic and metabolomic sequencing to identify the impact of diet on the microbiome. The effects on behaviour and cognition will also be determined.
- This program will provide measurable evidence on the gut-brain axis in the early stages of life.
This project is suitable for a PhD student.
Modulation of the microbiome to promote the maturation of the immune system in the perinatal period
Nearly one billion people globally suffer from allergies responsible for significant morbidity and reduced quality of life. Our group has discovered a process during the neonatal “Window of Opportunity” that prevents allergy from developing later in life. We propose to understand the mechanisms that allow neonates to become resistant to allergen sensitisation. This project will allow us to develop a novel and revolutionary approach to the management of allergic diseases. We will use a combination of experimental and clinical resources to address the role of the immune cells populating the gut and gut-associated tissues, which will be visualised by Flow cytometry and fluorescence imaging. We will use techniques like metagenomic sequencing, metabolomics and proteomics to determine the interaction between the microbiome – intestinal epithelium – immune cells.
This project is suitable for a PhD student.
Role of parasitic infection in early life on the development of allergic diseases
The Western lifestyle, characterised by a nutrient-poor diet, sedentary lifestyle, and exposure to antibiotics / pollution, and the Hygiene Hypothesis have been directly implicated in the development of allergic diseases. Parasites, such as hookworms, modulate the microbiome and provide important maturation signals to the immune system that result in protection against allergy. We are performing a cohort study on mothers and babies (up to 2 years of age) from hookworm-endemic and hookworm-eradicated areas to determine the influence of intestinal parasites on the microbiome composition and the development of allergic diseases. This exciting project will use a range of wet-lab, statistical and computational skills.
This project is suitable for a PhD student.
Development of a novel therapeutic pipeline for the treatment of inflammatory diseases
We have discovered hookworm proteins and peptides able to modulate the immune response and protect against allergic and autoimmune diseases (like IBD and colitis). We are interested in developing these novel compounds into the clinics and determine how the proteins alter cellular function. Gut-resident dendritic cells are the primary target and epigenetic modifications are likely to occur. This project will use a range of immunological techniques (experimental models, flow cytometry, fluorescence imaging), proteomics approaches (mass spectrometry), and single cell sequencing / metabolomics to characterise the mechanism of action.
This project is suitable for a Master, Honour or PhD student.
- Longevity of anti-parasitic and tolerogenic immune responses to malaria in humans
- Single cell genomic technologies in human malaria immunology
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