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.
Global Atopic Dermatitis Atlas (GADA)
Grantee: Carsten Flohr, King's College London
Amount: DKK 10,000,000
Grant category: Standalone grants
Year: 2023
Geography: United Kingdom
Atopic dermatitis, also called atopic eczema, or just eczema, is a non-contagious, chronic skin disease, causing dry, patchy, and itchy skin. It affects up to 20% of children and up to 10% of adults. Of all skin diseases worldwide, it is the most common type, with a burden that remains a significant challenge for the people affected, their families, and societies.
Despite progress made in treating severe forms of atopic dermatitis, there is a need for high-quality information showing how many people per country have atopic dermatitis and how severe it is. With strong data, atopic dermatitis can be better understood and treated.
With a grant from the LEO Foundation, the Global Atopic Dermatitis Atlas, or GADA, will help address gaps in current data by creating and maintaining a living online atlas, where the newest research-based knowledge and data on atopic dermatitis, its prevalence, severity, and treatment are available in one place – collected and analyzed in the same way for all countries.
About GADA
The Global Atopic Dermatitis Atlas (GADA) is a worldwide, long-term project. GADA is led by Professor Carsten Flohr (St John’s Institute of Dermatology, King’s College London, UK) and is an initiative established by the International League of Dermatological Societies (ILDS) in 2022 in collaboration with supporting stakeholders:
On track (På sporet – elever i 2. klasse lærer tal og algebra med læringsspor)
Grantee: Charlotte Skott, Professionshøjskolen Absalon
Amount: DKK 2,500,872
Grant category: Education and Awareness Grants
Year: 2023
Geography: Denmark
This project aims to apply a new research-based approach to enhance the teaching of mathematics in Denmark (called learning trajectories or Læringsspor in Danish), involving second-grade students and their mathematics teachers in all the public schools of Kalundborg as a first case. Learning trajectory constitutes an approach to numbers and algebra which has achieved promising results in international research. During the project, the Kalundborg mathematics teachers will learn about the approach and learning trajectories and be involved in developing educational material suited for a Danish context.
Science in reality (Videnskab i virkeligheden)
Grantee: Marie Erbs Ørbæk, CPH:DOX
Amount: DKK 980,000
Grant category: Education and Awareness Grants
Year: 2023
Geography: Denmark
CPH:DOX’s UNG:DOX program currently covers the greater Copenhagen area with a natural science educational focus during the two-week annual documentary film festival in March. Plans are underway to expand UNG:DOX to cover youth educations all over Denmark, providing year-round access. UNG:DOX offers upper secondary level students science documentaries from its international program, through streaming or live events, accompanied by expert lectures, scientist interviews, and additional resources for teachers.
Natural Science Marathon (Naturfagsmarathon)
Grantee: Maiken Lykke, Naturvidenskabernes Hus
Amount: DKK 2,000,000
Grant category: Education and Awareness Grants
Year: 2023
Geography: Denmark
This project continues the established ‘Naturfagsmaraton’ which provides a practice-oriented, engineering-inspired approach to STEM education with competitions revolving around real-world challenges, developed in collaboration with Danish companies. The project expands the current program aimed at 5th-6th grade pupils with an annual mini-marathon tailored for younger pupils.
The Science Olympiads (Science Olympiaderne)
Grantee: Niels Hartling, Science Olympiaderne
Amount: DKK 1,800,000
Grant category: Education and Awareness Grants
Year: 2023
Geography: Denmark
The Science Olympiads aim to stimulate the interest of Danish high school students in the fields of chemistry, physics, mathematics, biology, geography, and computer science. The Olympiad builds on six tracks – one in each of the six fields – which each follow the same structure, kicked off with annual nationwide competitions. Around 20,000 students participate in the national competitions, often as an integrated part of their high school education. The most talented students can qualify to participate in the international Science Olympiads. The Science Olympiads challenge gifted students to expand their talent, promote future careers in science, and provide them with a valuable network of peers
Influence of dietary derived gut microbial metabolites on skin barrier and atopic dermatitis development in early life (Infant AD)
Grantee: Clarissa Schwab, Associate Professor, Aarhus University
Amount: DKK 3,910,741
Grant category: Research Grants in open competition
Year: 2023
Geography: Denmark
Clarissa Schwab’s project aims to investigate the role of switching from liquid to solid diet in the development of AD during infancy.
Atopic dermatitis (AD) is one of the first manifestations of allergic diseases that occur in early life. In industrial countries, up to 30% of children suffer from AD imposing an enormous burden to the quality of life and to health systems.
Not all factors contributing to the occurrence of AD are known, but the development of the gut microbiota in relation to a switch from liquid to solid diet during the first year of life might play an important role.
This project, ‘Infant AD’, suggests that a combination of specific food components and the appearance of certain gut bacteria is critical to producing gut metabolites that affect the immune system, and ultimately the state of the skin. To tackle such a complex system at the interface of diet, microbiome and the host, the concept of Infant AD is based on a unique combination of microbial and/or nutritional intervention studies using in vitro and in vivo models with state-of-the-art microbiome and metabolome analysis that will be supported by data collected from the Swiss birth cohort Childhood, Allergy, Nutrition and Environment (CARE).
Infant AD may shed further light on the complex interactions between diet, microbial activity and the immune system that could lead to novel measures to lower the risk of AD development in infancy.
Microbial impact on vitiligo development
Grantee: Caroline Le Poole, Professor, Northwestern University
Amount: DKK 2,979,828
Grant category: Research Grants in open competition
Year: 2023
Geography: USA
Caroline Le Poole’s project aims to investigate the potential link between the gut microbiome composition and vitiligo development.
The etiology of vitiligo involves a complex hereditary component, as well as environmental factors that precipitate disease. Caroline Le Poole and her team initially asked whether the gut microbiome impacts T cell-mediated autoimmune depigmentation. Manipulating the gut microbiome by oral antibiotics, they demonstrated a significant impact on vitiligo development in an established mouse model of the disease. Specifically, when using ampicillin to favor gut colonization by Pseudomonas species, they observed accelerated vitiligo development. Meanwhile, neomycin treatment was associated with an abundance of Bacteroides species in the gut, while mice in this group did not develop measurable depigmentation. These and other findings suggest that specific microbes can influence vitiligo development.
Here, they will test the hypothesis that the microbiome is a causative pathogenic factor fueling the autoimmune response to melanocytes causing the hallmark progressive depigmentation seen in vitiligo. The team will use mouse and human fecal transplants and manipulate the diet of vitiligo-prone mice. Moreover, individual microbial species will be introduced into germ-free mice before assessing depigmentation kinetics. Ultimately, therapeutic benefit may be derived from promoting the species that support regulatory T cell activity.
Striving to develop and implement culturally sensitive dermatologic care with the focus on eczema and psoriasis in the Cree Territory of James Bay (Eeyou Istchee)
Grantee: Ivan Litvinov, Associate Professor, McGill University Health Centre
Amount: DKK 3,074,290
Grant category: Research Grants in open competition
Year: 2023
Geography: Canada
Ivan Litvinov’s project aims to co-create with Indigenous partners and implement a culturally sensitive dermatological care system in the Cree territories in Quebec, one of Canada’s First Nations. Dermatologic care for Canadian Indigenous populations is severely lacking currently. While many safe advanced treatments are available for debilitating diseases, including atopic dermatitis that affects ~15-20% of First Nations in Quebec, these treatments are not accessible in the Northern remote regions due to a lack of established care.
Ivan Litvinov’s proposed implementation science project will be centered on meaningful engagement of patients, health care providers (HCPs) and wider communities, continuous monitoring, analysis, and feedback based on collected data to the members of the steering committee and to the Cree Health Board/Elders overseeing the effort with the goal of achieving the Quintuple Aim (improved patient experience, better outcomes, lower costs, clinician well-being and health equity) for the region.
Ivan Litvinov’s project will leverage the existing RUISSS (Réseau Universitaire Intégré de Santé et de Services Sociaux) infrastructure to establish in-person care in 3 key Cree communities and will 1) establish a Learning Healthcare System (LHS); 2) collect quantitative and qualitative data on skin diseases, barriers and treatments; 3) recruit and support healthcare professionals to the region to foster a community of practice and promote a community of concern amongst patients through Patient and Public Involvement, knowledge mobilization and educational activities.
The impact of the project will be a co-creation of a culturally sensitive sustainable dermatologic care in the region. Results of this work will be shared with other specialties working in the region, other First Nation communities in Quebec in Canada and in other countries (e.g., Greenland).
High-resolution identification of bacterial-host interactions in atopic dermatitis during flare development and treatment
Grantee: Blaine Fritz, Postdoc, University of Copenhagen
Amount: DKK 2,956,179
Grant category: Research Grants in open competition
Year: 2023
Geography: Denmark
Blaine Fritz’s project investigates the ongoing genetic changes and interactions between bacteria and patients’ skin during development of atopic dermatitis to identify novel putative treatment targets.
Atopic dermatitis (AD) is one of the most common skin diseases, affecting up to 20% of children and 10% of adults. AD presents as localized, itching patches of eczema, frequently first observed during childhood and often persisting throughout the patient’s life.
Dysregulated immune response, microbial imbalances, and skin barrier dysfunction are among several, interacting factors, which invoke and perpetuate AD. In up to 90% of patients, aggressive pathogens such as Staphylococcus aureus displace the protective microbiota of the skin resulting in reduced microbial diversity and increased lesion severity. Clinicians commonly utilize antibiotics to treat bacterial infection in AD, but the efficacy is unclear and antibiotic treatment increases the probability of resistance.
The mechanisms and specific gene targets involved in host-microbial interactions by both commensal (non-pathogenic) and infecting bacteria are not well studied. This project hypothesizes that both protective and pathogenic bacteria on the skin dynamically activate specific host-genes and pathways during progression of an AD flare. To test this hypothesis, Blaine Fritz will utilize an integrated, machine-learning-based approach to identify longitudinal (i.e., over time) changes in gene-expression associated with the presence of specific bacteria during flare and treatment to identify direct, host-microbial interactions.
The findings will aid in elucidating bacteria’s role in AD and may guide antibiotic treatment, as well as identify novel targets for antibiotic-independent treatments.