Spotlight on EMCR Awardees 2021/2022

In 2021/22, WHRTN awarded 36 EMCRs grants for flexible and diverse needs, and to strengthen and boost career development.  Read about the projects from awardees Dr Emily Camm and Dr Margret Jordan.

A further 32 ECR women will be supported by funding in 2023.

Dr Emily Camm

Developmental neurophysiologist, The Ritchie Centre (Hudson Institute of Medical Research)

To establish the morphological and mitochondrial phenotype of the placenta in overweight and obese women.

“The funding has provided invaluable seed funding to generate critical pilot data for larger grant funding applications, whilst enhancing my research portfolio and track record, thereby making me more competitive in future grant funding applications. I have also benefited from being connected to the AHRA Women's Health Research Translation and Impact Network, where I have attended several professional development and leadership seminars”

Project overview

Aim -

Over 74,000 women are diagnosed with cancer each year. Due to improvements in cancer treatment (surgery, chemotherapy, radiotherapy) and the proliferation of long-term cancer survivors (75-91% 5-year survival rates), women are more likely to die of heart disease than their cancer. There is limited heart health support for cancer survivors between medical appointments and a co-designed solution was urgently needed.

A high maternal body mass index (BMI) before pregnancy is known to increase the risk of pregnancy complications, and adversely affect both fetal growth and later-life health of the newborn. The mechanisms linking maternal BMI to later health outcomes in children are poorly understood, preventing the implementation of effective strategies and early interventions. The placenta, the master regulator of the fetal environment that provides the nutrients, hormones and growth factors essential for intrauterine growth and development, is a valuable resource for the investigation of processes involved in the developmental programming of offspring health.

Rationale

The mechanisms via which maternal obesity increases the risk for programming of offspring disease remains unknown. The placenta, specifically placental mitochondria, which fuel placenta growth and development, may provide this link.

Dr Margaret Jordan

Senior Research Fellow in Molecular & Cell Biology at JCU in the College of Public Health, Medical and Veterinary Sciences.

 Generate a pilot dataset of immune cell subset and gene interaction network involvement during initiation of disease in EAE, an animal model of human MS, to better understand the underlying mechanism of disease.

“This has afforded me the opportunity to produce much-needed preliminary data to apply for further financial support for my research.  It has allowed me to test the feasibility of using a new and extremely powerful genomic technique that is at the forefront of techniques used today for elucidating gene interactive pathways and the cell subsets involved, to uncover functional aspects of gene manipulation. Given the costs involved, this would not have been possible without this grant.“

Project Overview

Multiple Sclerosis (MS) is an autoimmune disease in which discrete central nervous system (CNS) lesions result from perivascular immune cell infiltration associated with damage to myelin (demyelination), oligodendrocytes and neurons. It is the most prevalent neurological disease among young adults in developed countries, with approximately 2.8 million people being affected worldwide.

It principally affects women in their prime, with diagnosis typically occurring between the ages of 20 and 40. The disease is debilitating due to CNS damage resulting from activated lymphocytes migrating across the blood brain barrier (BBB) and engaging in a proinflammatory response. This causes cells to attack and destroy the myelin sheaths that coat the axons of neurons of the brain, spinal cord and optic nerve, as well as the myelinating cells or oligodendrocytes, and the axons themselves.

Although there are many treatments available today, not all have equal efficacy, they can cause side effects, and there is no cure. Additionally, the identity of the immune cells that initiate the autoimmune attack in MS is disputed, so research to elucidate this will help provide important information regarding disease initiation/progression.  Knowing which major gene pathways and interactive networks are involved will inform potential areas for intervention and the development of targeted therapeutics, and this is the focus of our research. 

To date, we have generated a gene interactive network analysis of five major leucocyte subsets from 67 Relapsing Remitting (RR) MS patients and 102 Health Controls. Here we have identified a major networked module of genes involved in cell-mediated cytotoxicity that is downregulated in the monocytes of MS patients (our unpublished data). In order to identify the underlying mechanisms involved, we downregulated this module in monocytes during disease progression in a mouse model of disease (EAE, experimental autoimmune encephalomyelitis), and adopted the Chromium 10x system, an innovative technology that enables high-throughput single cell analysis (scSequencing), as a means of providing us with preliminary single cell immune profiling data, to give an overall picture of in vivo gene expression changes and their associated pathways due to the targeted manipulation of the module (pilot study).

This technique is at the forefront of technologies today to identify gene expression changes at the single cell level. Although extremely powerful, it is also extremely costly and requires careful experimental design, and the preparation of good quality samples, including those with high viability post freeze-thaw. We have successfully mastered these techniques and prepared experimental and control samples for scSequencing at the Australian Genome Research Facility (AGRF). We analysed the resulting dataset using bioinformatic tools of Cell Ranger, Loupe Browser and the R package Seurat.

This pilot data has not only provided us with essential information regarding differential expression, cell subset involvement and interactive gene networks during disease initiation but has also provided us with evidence of the feasibility of this technique, to examine the target module of interest.

The results from the pilot study will now be used to apply for a larger grant so that a more extensive project can be undertaken to provide us with a clearer picture of the underlying differential gene state of the pathogenesis of disease.  This will help provide not only a new perspective on the aetiology of MS, but also provide crucial information important in understanding other neurological diseases and other complex autoimmune diseases, so that novel interventions may be revealed. Our pilot data produced here will provide the evidence needed to prove our expertise in the technology and this will strengthen our application.