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- A new regulator of 'stemness' to create dendritic cell factories for immunotherapy
- Advanced imaging interrogation of pathogen induced NETosis
- Cancer driver deserts
- Cryo-electron microscopy of Wnt signalling complexes
- Deciphering the heterogeneity of breast cancer at the epigenetic and genetic levels
- Developing drugs to block malaria transmission
- Developing new computational tools for CRISPR genomics to advance cancer research
- Developing novel antibody-based methods for regulating apoptotic cell death
- Discovering novel paradigms to cure viral and bacterial infections
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Do membrane forces govern assembly of the deadly apoptotic pore?
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- E3 ubiquitin ligases in neurodegeneration, autoinflammation and cancer
- Engineering improved CAR-T cell therapies
- Epigenetic biomarkers of tuberculosis infection
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- Genomic rearrangement detection with third generation sequencing technology
- How does DNA damage shape disease susceptibility over a lifetime?
- How does DNA hypermutation shape the development of solid tumours?
- How platelets prevent neonatal stroke
- Human lung protective immunity to tuberculosis
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigating the role of dysregulated Tom40 in neurodegeneration
- Investigating the role of mutant p53 in cancer
- Lupus: proteasome inhibitors and inflammation
- Machine learning methods for somatic genome rearrangement detection
- Malaria: going bananas for sex
- Measurements of malaria parasite and erythrocyte membrane interactions using cutting-edge microscopy
- Measuring susceptibility of cancer cells to BH3-mimetics
- Minimising rheumatic adverse events of checkpoint inhibitor cancer therapy
- Mutational signatures of structural variation
- Naturally acquired immune response to malaria parasites
- Predicting the effect of non-coding structural variants in cancer
- Revealing the epigenetic origins of immune disease
- Reversing antimalarial resistance in human malaria parasites
- Structural and functional analysis of DNA repair complexes
- Targeting human infective coronaviruses using alpaca antibodies
- Towards targeting altered glial biology in high-grade brain cancers
- Uncovering the real impact of persistent malaria infections
- Understanding Plasmodium falciparum invasion of red blood cells
- Understanding how malaria parasites sabotage acquisition of immunity
- Understanding malaria infection dynamics
- Understanding the mechanism of type I cytokine receptor activation
- Unveiling the heterogeneity of small cell lung cancer
- Using alpaca antibodies to understand malaria invasion and transmission
- Using combination immunotherapy to tackle heterogeneous brain tumours
- Using intravital microscopy for immunotherapy against brain tumours
- Using nanobodies to cross the blood brain barrier for drug delivery
- Using structural biology to understand programmed cell death
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Alyssa Barry-Projects
Researcher:
Genomic surveillance of malaria parasite populations and outbreaks
With many countries scaling up their malaria control efforts and attempting elimination there is an urgent need for molecular surveillance to map parasite transmission. This knowledge could be used to deploy resources appropriately and to reduce the risk of imported infections.
We are mapping the distribution and spread of malaria infections in malaria endemic countries to provide insight into the spatial and temporal patterns of transmission, and a basis upon which to identify the origins of outbreaks in eliminating areas.
The research will facilitate malaria control and elimination efforts in the region by identifying regions where targeted control will be most effective.
Project resources
2016 Genome technology boosts malaria control efforts
Team members
Abebe Fola, Zahra Razook
Understanding the roles of polymorphism in leading malaria vaccine candidates
This project aims to advance our understanding of the function of different parasite antigens and provide critical data for their development as vaccine candidates.
Sequence data from a large number of P. falciparum and P. vivax isolates is being generated to measure genetic diversity and signatures of natural selection, followed by 3D protein modeling and in vitro assays to gain insight into the functional implications of polymorphism.
In addition, we are investigating samples from longitudinal cohorts of children to identify correlates of immunity and parasite genetic determinants of immune escape. The resulting information will be used in the development of parasite antigens as vaccine candidates and to maximize their ability to target all strains.
Project resources
2016 Genome technology boosts malaria control efforts
Team members
Digjaya Utama, Elijah Martin
Defining correlates of naturally acquired immunity to severe malaria
Humans that are constantly exposed to malaria eventually develop immunity against all of the clinical symptoms of the disease. Uncovering molecular targets of this immunity may lead to a malaria vaccine and new diagnostic tools for monitoring immunity in human populations.
Antibodies against the major surface antigen of Plasmodium falciparum, known as Erythrocyte Membrane Protein 1 (PfEMP1) are protective against severe disease however there are many different variants of this protein expressed by individual parasite clones, and each parasite clone has a unique repertoire of PfEMP1 variants. In order to identify the critical protective antibody responses we have developed a protein microarray approach to investigate antibody responses to large numbers of PfEMP1 variants in parallel.
We are using this approach to investigate antibody response patterns in a cohort of young children from Papua New Guinea to identify correlates of protection against severe malaria.
Team member
Digjaya Utama
Understanding host-pathogen interactions in clinical and severe malaria
Uncovering molecular targets of natural immunity to malaria and the host molecules that they interact with may lead to new vaccines and diagnostic tools.
P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) is a major immune target however extreme genetic diversity amongst these antigens has complicated vaccine development. In order to identify the critical protective antibody targets we have developed a protein microarray approach to investigate antibody responses to large numbers of PfEMP1 variants in parallel.
We used this approach to investigate antibody response patterns in a cohort of young children from PNG to identify targets of protective immunity. We are now investigating the impact of genetic polymorphism in PfEMP1 receptors such as EPCR, CR1 and ICAM1. We are also interested in the involvement of other variant surface antigens in clinical and severe malaria.
Team member
Digjaya Utama
Novel biomarkers and mechanisms of antimalarial drug resistance
The emergence of resistance to current frontline antimalarial drugs is a major global health emergency that threatens to undermine malaria control programs, reverse progress towards elimination and risks millions of lives.
Through analysis of thousands of P. falciparum genomes, we have discovered novel regions of the genome that may underlie drug resistance. We now aim to identify the gene mutations involved, to discover new drug resistance biomarkers and to understand mechanisms of resistance.
The project employs genomic epidemiology, molecular parasitology and systems biology approaches. Identification and validation of novel biomarkers of resistance will lead to improved surveillance and help optimize strategies to control resistant parasites.
Project resources
2016 Genome technology boosts malaria control efforts
Team members
Abebe Fola, Zahra Razook