Six EMBL Australia group leaders have been awarded more than $4.3 million in funding for their innovative research through the National Health and Medical Research Council (NHMRC)’s Ideas Grant scheme.
Professor David Lynn, Associate Professor Chen Davidovich, Dr Michelle Boyle, Dr Senthil Arumugam, Dr Maté Biro and Dr Harald Janovjak were each awarded a competitive Ideas Grant, the outcomes of which were announced this week.
The funding will support innovative and diverse research by our group leaders, including the investigation of the role of the gut microbiota in regulating the efficacy and toxicity of cancer immunotherapy drugs, the manipulation of T-follicular helper cells to improve human malaria vaccines and research into how chromatin-modifying enzymes are regulated at the molecular level.
Summaries of each project are below.
PROFESSOR DAVID LYNN (SOUTH AUSTRALIAN HEALTH AND MEDICAL RESEARCH INSTITUTE (SAHMRI) AND FLINDERS UNIVERSITY)
Title: ‘Targeting the gut microbiota to improve the safety and efficacy of agonistic cancer immunotherapies’
Total: $704,312
Field of research: Tumour Immunology
Description: Immunotherapies boost immune system functions, driving both beneficial anti-cancer responses and detrimental adverse immune events. Uncovering the intrinsic host factors that influence these responses is critical to improve patient outcomes following therapy. This proposal will explore how our gut bacteria alters immune responses to agonistic immunotherapies and use these findings to design microbiota targeted therapies to augment their activity, improving both safety and efficacy of treatment.
DR MATÉ BIRO (THE UNIVERSITY OF NEW SOUTH WALES)
Title: ‘Harnessing homotypic T cell chemokine signalling to enhance solid tumour infiltration’
Total: $860,076
Field of research: Solid Tumours
Description: The ability of killer T cells to find and eliminate tumour cells is the basis for adoptive transfer immunotherapies, which thus far only work well with blood-borne cancers. There is limited success with solid tumours, which T cells do not readily infiltrate. We have discovered a direct communication mechanism that enables T cells that recognise a tumour cell to recruit distant T cell populations. Here, we will harness this discovery to improve tumour infiltration and rejection of solid tumours.
DR MICHELLE BOYLE (QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE)
Title: ‘Manipulating T follicular helper cells to improve human malaria vaccines’
Total: $742,700
Field of research: Medical Parasitology
Description: The World Health Organisation has set the goal for a malaria vaccine with >75% efficacy by 2030. To reach this goal, innovative and unbiased approaches are required. We will investigate the activation of a specific cell involved in vaccine efficacy known as T-follicular helper cells. We will use human clinical samples and apply the best available technologies to understanding the activation of this cell in malaria. Our data will identify ways to manipulate this cell subset to improve vaccines.
A/PROF CHEN DAVIDOVICH (MONASH BIOMEDICINE DISCOVERY INSTITUTE)
Title: ‘Mechanism for LCOR-mediated regulation of the histone methyltransferase PRC2: a new hotspot in a sought-after target’
Total: $713,880
Field of research: Structural Biology (incl. Macromolecular Modelling)
Description: Thousands of genes are maintained in an off-state in all cell types and all multicellular organisms. The process of maintaining genes in an off-state requires chemical modifications of proteins in their immediate vicinity. PRC2 is a key protein complex that modifies proteins at the immediate vicinity of genes, in order to keep these genes off in healthy cells, but PRC2 is often dysregulated in disease. The project aims to understand how PRC2 is regulated by another protein, called LCOR.
DR SENTHIL ARUMUGAM (MONASH BIOMEDICINE DISCOVERY INSTITUTE)
Title: ‘The HIV capsid is a functional scaffold that directs bidirectional cargo transport’
Total: $820,337
Field of research: Protein Trafficking
Description: HIV carries its genetic material inside a protective shell called the capsid. Once it has invaded a human cell, the capsid hijacks motor proteins from the host cell for transporting its genetic material to the nucleus. Interestingly, both motors walking towards the nucleus as well as those walking in the opposite direction are needed. By resolving how the movement of opposing motors is coordinated, we will better understand how transport inside cells works and have a new angle for targeting HIV.
DR HARALD JANOVJAK (AUSTRALIAN REGENERATIVE MEDICINE INSTITUTE AT MONASH UNIVERSITY)
Title: ‘Beta-cell replication through light activation of the OPN3 receptor’
Total: $465,185
Field of research: Signal Transduction
Description: Beta-cells are a group of cells that are located in the pancreas and essential for maintaining proper blood sugar levels. Death of beta-cells is a hallmark of diabetes, and new methods to protect beta-cells are urgently needed. We recently discovered that beta-cells respond to visible light with improved survival using proteins from the visual system. In this project, we will develop a new light-based strategy to increase the number and activity of beta-cells in isolation and animal models.
While 294 projects from across the country will be funded, only 11 per cent of grant applications were successful.
The objective of the NHMRC Ideas Grant scheme is to support innovative research projects addressing a specific question.