Accelerating to Zero Transmission of Leprosy in Nepal (ACCELERATE)

Grantee: Sarah Dunstan, Principal Research Fellow, University of Melbourne

Amount: DKK 4,000,000

Grant category: Research Grants in open competition

Year: 2023

Geography: Australia

Sarah Dunstan’s project aims to whole-genome sequence the leprosy-causing bacteria (Mycobacterium leprae) found in specific areas of Nepal to understand disease epidemiology, transmission dynamics and persistence to improve treatment strategies.

Leprosy, a neglected tropical disease of the skin, causes severe stigmatization, long term disability and mental health issues. It is treatable and preventable yet persists among the world’s poorest and most neglected citizens. To realize the goal of a leprosy-free world we need to deepen the knowledge of the disease pathophysiology and how it spreads, and ensure effective strategies to diagnose, prevent, and cure the disease and its long-term effects. Major gaps exist in the understanding of leprosy transmission which limit the efficiency of interventions to prevent infections and achieve zero transmission.

Sarah Dunstan’s project will use whole genome sequencing of the causative agent, Mycobacterium leprae, to unravel the complexities of leprosy epidemiology and persistence. The knowledge gained will also improve interventions for diagnosis, treatment, and vaccine strategies, and develop a robust framework for obtaining the zero-transmission goal in Nepal. A network of community health workers will conduct active case finding for leprosy in the community in two districts of Nepal with a high incidence of leprosy and high multidimensional poverty index (i.e., poverty in relation to health, education and living standards). Genomic epidemiology will be used to characterize subtypes of the M. leprae identified, matched to individual patients, disease transmission dynamics and drug resistance emergence. Mathematical models will inform optimized active case finding, and this will form the basis of stakeholder engagement to develop evidence-informed policy revisions in the national strategic plan for leprosy.

Unravelling the diversity and function of skin-resident T cells

Grantee: Laura Mackay, Professor, University of Melbourne

Amount: DKK 3,826,119

Grant category: Research Grants in open competition

Year: 2023

Geography: Australia

Laura Mackay’s project investigates how tissue-resident T cell (TRM) populations in skin vary in development and function across body surfaces exposed to different environmental factors.

The generation of optimal immunotherapies requires effective T cell responses. Whilst some T cells patrol the blood, a unique subset called tissue-resident memory T (TRM) cells permanently exist within the tissues of the body. T cells that reside in the skin comprise distinct populations that differentially contribute to protecting the skin against disease.

The previous work of Laura Mackay and her team has demonstrated that different populations of skin-resident T cells in mice rely on separate molecular processes to function effectively. However, understanding of how human skin-resident T cells develop and control infectious insults and inflammatory disorders remains limited.

This project aims to determine skin TRM cell variation across the body, encompassing skin sites exposed to different environmental factors, such as sun exposure and hair follicle density, as well as in the context of disease. The team will seek to define the molecules that enhance skin-resident T cell function and survival, thus identifying factors that may prevent disease in healthy skin.

Overall, the aim is to generate fundamental new knowledge about the regulation of skin immunity and homeostasis. This knowledge is critical for the development of treatments and immunotherapies to harness T cell immunity for skin disorders.

The LEO Foundation Award 2023 – Region Asia-Pacific

Grantee: Dr. Laura Mackay, Professor, The University of Melbourne

Amount: USD 100,000

Grant category: LEO Foundation Awards

Year: 2023

Geography: Australia

Dr. Laura Mackay is a Professor at The University of Melbourne in Australia.

She receives the award for her momentous work within the field of immunological memory, as she continues to build upon her own research shedding light on how tissue-resident T cells provide first-line defense against infection.

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En route to identifying peptide antigen triggers in psoriasis

Grantee: Asolina Braun, Senior Research Fellow, Monash University

Amount: DKK 4,007,900

Grant category: Research Grants in open competition

Year: 2022

Geography: Australia

Asolina Braun, along with her team and colleagues Professor Anthony Purcell and Professor Johannes Kern, aims to identify and characterize the key self-antigens presented to autoreactive T-cells in psoriasis (PsO) patients. Specifically, she will look at molecules displayed by the major psoriasis genetic risk determinant to identify new treatment targets.

Psoriasis is believed to be an autoimmune disease in which T cells of the immune system recognize short protein sequences (antigens) from the body’s own cells and subsequently attack and destroy tissues inducing a chronic state of inflammation. The initial priming of the T-cells occurs when antigens are presented on the surface of cells by human leukocyte antigen (HLA) receptors, the same molecules that need to be matched in organ transplantations. Among the HLA molecules, the HLA-Cw6+ variant is particularly abundant in psoriatic patients (50% of all and 80% of early onset patients), and Asolina and her team aim to characterize the specific antigens presented by this particular HLA receptor to identify potential targets for future immune therapy like the induction of tolerance in food allergies. The team has already generated the peptide (antigen) library necessary to investigate targets and has created a transgenic mouse model containing the desired HLA receptor to present the antigens. They will also use patient-isolated T-cells to examine the responses and identify the most important peptide antigens contributing to the disease. In parallel, they will investigate if the original trigger of the autoimmune response is caused by peptides from virulent (disease-causing) strains of the environmental pathogenic bacteria, Streptococcus pyrogenes.

The Human Skin Immune Atlas: Three-dimensional reconstruction of serial histology and computational image analysis of dermal immune populations in normal and diseased skin

Grantee: Philip L. Tong, PhD, Department of Dermatology, Royal Prince Albert Hospital, University of Sydney, Australia, Dr Ben Roediger and Professor Wolgang Weninger, Centenary Institute, Newtown, Australia, and Dr Weimiao Yu, Institute of Molecular and Cell Biology, A*STAR, Singapore

Amount: DKK 708,500

Grant category: Research Grants in open competition

Year: 2016

Geography: Australia, Singapore

This research project, led by Dr Philip Tong from the University of Sydney, has the potential to represent a technological advancement in the field of human skin immunological research. By use of 3D histological reconstruction and computational image analysis, the aim is to develop the world’s first Human Skin Immune Atlas of dermal immune populations in normal and diseased skin.

The members of the team assembled for this project are already established experts in the fields of skin immunology, microscopy, inflammation and computational analysis, and the project will have an international platform with sites across Asia and Oceania.

The skin is a complex organ, wherein topographical and micro-compartmental specialisation of the immune system has been demonstrated. The general spatial understanding of the skin immune system has been advanced through the use of transgenic laboratory animals with live imaging tools. These, however, have yet to be validated in humans. The work realised in this project may provide fundamental insights into the human skin immune system.

Moreover, the data generated may have wide reaching implications for the development of better in vitro skin substitutes, validation of in vivo microscopic skin imaging tools for human use and improved quantification of skin inflammation in clinical trial settings.

The natural history of skin cancer formation: from normal skin to cancer

Grantee: Associate Professor Kiarash Khosrotehrani, University of Queensland

Amount: AUD 268,239

Grant category: Research Grants in open competition

Year: 2015

Geography: Australia

Associate Professor Kiarash Khosrotehrani from The University of Queensland leads a team that has hypothesized that upon UV irradiation and acquisitions of mutations, only epidermal cells that can rapidly proliferate are likely to give rise to pre-cancerous and cancerous lesions.

This hypothesis will be tested using multicolour lineage tracing to follow simultaneously multiple epidermal clones that will further be microdissected to establish their mutational profile.  This study has the potential to fundamentally change our understanding of field cancerisation, cell of origin of squamous cell cancer establishing potentially new therapeutic targets.

Preventing Basal Cell Carcinoma formation by targeting the tumor environment

Grantee: Associate Professor Kiarash Khosrotehrani, University of Queensland

Amount: AUD 415,386

Grant category: Research Grants in open competition

Year: 2015

Geography: Australia

In this study, Associate Professor Kiarash Khosrotehrani of The University of Queensland in Australia proposes to better characterise the molecular nature of the factors provided by fibroblasts to support basal cell carcinoma (BCC) growth in vivo in order to find new targets for therapies that would prevent BCC development. He and his team will also show proof of principle demonstrating that targeting this process can actually prevent BCC development.

These findings have the potential to translate in effective prevention strategies, allowing field therapy of normal looking skin to avoid the development of new BCCs. Such finding will have strong health benefits in terms of morbidity associated with multiple surgeries, years of healthy life enjoyed by individuals and finally in terms of economic cost.

The LEO Foundation Scholarship for Dermatological Research

Grantee: Scholarship programme

Amount: DKK 2,200,000

Grant category: Research Grants in open competition

Year: 2012

Geography: Australia, Denmark

The LEO Foundation Scholarship for Dermatological Research aims to strengthen research collaboration within the field of skin cancer between Australia and Denmark by supporting training of and research by young scientists.

One scholarship is offered annually on behalf of the LEO Foundation, alternating between Australia and Denmark.

A candidate from Australia travels to work within a Danish tertiary institution and a Danish student is selected with a view to joining an Australian campus.

The funds received may be used as part of an ongoing PhD project or for postdoctoral research. The funds must in part support a research/educational stay in Australia of at least six months for the Danish student.

Publications

Automated detection of actinic keratoses in clinical photographs

Hames SC, Sinnya S, Tan JM, Morze C, Sahebian A, Soyer HP, Prow TW.

PLoS One. 2015 Jan 23;10(1):e0112447. doi: 10.1371/journal.pone.0112447. eCollection 2015

Counting actinic keratosis – is photographic assessment a reliable alternative to physical examinations in clinical trials?

Sinnya S, O’Rourke P, Ballard E, Tan JM, Morze C, Sahebian A, Hames SC, Prow TW, Green AC, Soyer HP.

Acta Derm Venerol. 2015 May;95(5):604-5. doi: 10.2340/00015555-2040. No abstract avaliable

The future of keratinocyte skin cancer surveillance: automated image analysis to identify and monitor keratinocyte dysplasia

Hames SC, Prow TW.

Curr Probl Dermatol. 2015;46:77-84. doi: 10.1159/000366540. Epub 2014 Dec 18

Automated segmentation of skin strata in reflectance confocal microscopy depth stacks

Hames SC, Ardigò M, Soyer HP, Bradley AP, Prow TW.

PLoS One. 2016 Apr 18;11(4):e10153208. doi: 10.1371/journal.pone.0153208. eCollection 2016.

Automated detection of actinic keratoses in clinical photographs

Hames SC, Sinnya S, Tan JM, Morze C, Sahebian A, Soyer HP, Prow TW.

PLoS One. 2015 Jan 23;10(1):e0112447. doi: 10.1371/journal.pone.0112447. eCollection 2015.

Counting actinic keratosis – is photographic assessment a reliable alternative to physical examination in clinical trials?

Sinnya S, O’Rourke P, Ballard E, Tan JM, Morze C, Sahebian A, Hames SC, Prow TW, Green AC, Soyer HP.

Acta Derm Venereol. 2015 May;95(5):604-5. doi: 10.2340/00015555-2040. No abstract available.

The future of keratinocyte skin cancer surveillance: automated image analysis to identify and monitor keratinocyte dysplasia

Hames SC, Prow TW.

Curr Probl Dermatol. 2015;46:77-84. doi: 10.1159/000366540. Epub 2014 Dec 18

Anatomical skin segmentation in reflectance confocal microscopy with weak labels*

Hames SC, Ardigò M, Soyer HP, Bradley AP, Prow TW.

http://ieeexplore.ieee.org/xpls/abs_aa.jsp?arnumber=7371231&tag=1

* This won the Canon Extreme Imaging Competition (DICTA category) prize in late 2015