Grant geography: Denmark

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2023

Geography: Denmark

Project title: Staphylococcus aureus drives inflammation and disease activity in atopic dermatitis – novel approaches to old problems 

Fellowship theme: Skin Immunology and Inflammatory Skin Diseases

Terkild Brink Buus’ vision is to develop better strategies to manage Atopic Dermatitis (AD) and improve patient lives by increasing our understanding and providing vital insights into the underlying biology. AD is a debilitating disease affecting more than 30% of Danish children at great cost to patients, parents, and society.

Terkild Brink Buus’s project addresses the role of bacteria and their toxins in causing severe worsening of the AD. Building on his expertise in complex data analysis and research on aberrant T cells and skin inflammation, Terkild Brink Buus will explore how T cells – a vital part of our immune system – are hijacked by bacterial toxins to aggravate AD and how this can be counteracted by novel treatments.

Terkild Brink Buus hopes to increase our understanding of how bacteria and their toxins affect the skin and worsen the symptoms of AD patients. His research will provide the basis for initiating clinical trials of new treatment approaches targeting bacteria in AD patients as well as guidelines for how to determine which patients are most likely to benefit. Finally, he will provide several novel laboratory and analytical techniques that will be of high value to future research within inflammatory skin diseases.

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2023

Geography: Denmark

Project title – ILnext: Unravelling the potential of ionic liquids as next generation cutaneous drug delivery systems

Fellowship theme: Skin Physiology and Cutaneous Drug Delivery

Stine Rønholt’s vision is to explore new ways to treat chronic skin issues (like eczema) directly on the skin. Today, such diseases are primarily treated by immunosuppressants, that upon systemic exposure can weaken the immune system. Atopic dermatitis is effectively treated by a type of medicine called JAK inhibitors, administered as tablets. Yet, direct administration of JAK inhibitors via the skin is hampered by the skin’s tough outer layer.

Stine Rønholt’s project will develop a new technology that treats eczema directly on the skin. To do so, Stine Rønholt is using a novel approach, “ionic liquids,” which can increase the drug solubility allowing for high dose treatment. Much like how sugar dissolves in water. This approach will help to deliver more medicine into the skin, targeting and treating eczema more effectively. Stine Rønholt’s goal is to figure out how to make this work for two specific JAK inhibitors, baricitinib and abrocitinib. Focus here is currently directed towards understanding how the ionic liquids used work together with the drugs, as well as what happens to the skin when the drug is applied. Even though the drug needs to be transported across the skin to where it is going to work, the technology should not cause any irritability to the skin. Special biophysical techniques are to be used to study all these things closely.

Stine Rønholt hopes to be able to deliver a high amount of medicine directly to a problem area without any uncomfortable procedures by using this approach. This could enhance treatment and lower the frequency of medicine required. Additionally, insights gained from Stine Rønholt’s project may pave the way for a new and improved method of addressing skin issues in a more efficient manner.

Grant category: LEO Foundation Dr Abildgaard Fellowships

Year: 2023

Geography: Denmark

Project title – T-cell derived extracellular vesicles constitute pro-inflammatory packages that drive disease progression in psoriasis

Fellowship theme: Skin Immunology and Inflammatory Skin Diseases

Aida Hansen’s vision is to improve the treatment options for psoriasis patients by contributing to a more detailed understanding of the cellular cross-talk mediating the inflammatory processes in the disease. She aims to investigate a novel concept for cellular cross-talk, mediated by vesicular structures known as extracellular vesicles (EVs), that may drive inflammation in psoriasis.

Aida Hansen’s project builds upon knowledge that psoriasis is mainly driven by pro-inflammatory cytokines, and recently, it was discovered that cytokines are partly packaged into EVs. She hypothesizes that the majority of cytokines implicated in psoriasis are carried in specific subsets of EVs constituting “pro-inflammatory packages”. She will: 1) Do an in-depth investigation of the packaging of cytokines into EVs derived from patients with severe psoriasis, 2) Investigate the functional impact of specific EV-subpopulations in driving the inflammatory response in psoriasis, and 3) Explore the therapeutic concept for neutralizing specific disease-promoting EVs in psoriasis.

Aida Hansen hopes to contribute to a deeper understanding of how cytokines are being transported between cells and the potentially different biological properties of soluble cytokines compared to cytokines packaged into EVs. This is still poorly understood. The outcome of her project may lead to identification of new inflammatory pathways and novel depletion strategies for innovative therapeutic interventions to alleviate symptoms and improve the quality of life for patients with severe psoriasis.

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

The project led by Thomas Sicheritz-Pontén from the Globe Institute at the University of Copenhagen, aims to carry out the fundamental work needed to develop targeted phage therapy (using bacteria-infecting viruses) to counter Necrotizing Soft Tissue Infections (NSTI).  This innovative treatment approach necessitates an in-depth understanding of the causative organisms, which will be achieved through sequencing these organisms and employing machine learning algorithms to predict their susceptibility to specific phages.

Necrotizing Soft Tissue Infections (NSTI), also known as “flesh-eating disease”, are rapidly escalating globally, posing a deadly bacterial threat that necessitates innovative therapeutic strategies due to its profound impact on human health. NSTI is characterized by aggressive skin manifestations primarily caused by Group A Streptococcus (Strep A). Although prompt surgery and antibiotics serve as the first-line treatment, infections often progress to necrosis, rendering antibiotics ineffective and often necessitating amputation and in worst case death.

Bacteriophages, or simply phages, offer a promising avenue to address this severe skin and soft tissue infection. Phages are viruses that selectively infect and eliminate bacteria, including antibiotic-resistant strains, without harming human cells.

Thomas Sicheritz-Pontén and team will do the fundamental work needed to identify prototype tailored phage therapies targeting Strep A. Along with his team, comprised of chief physicians from three different Danish hospitals, the UK Centre for Phage Research and the University of Copenhagen, Thomas Sicheritz-Pontén intends to identify phages capable of rapidly eradicating the bacteria, harness bacterial enzymes (endolysins), and employ phage satellites (mobile genetic elements that parasitize phages) for gene delivery.

By collaborating across research hubs, the team will decode Strep A’s genetic makeup, thereby facilitating the creation of precise phage cocktails and develop a novel molecular typing system to predict bacterial susceptibility, streamlining targeted phage treatments.

If successful, Thomas Sicheritz-Pontén’s project may greatly aid the battle against deadly NSTI infections through innovative development of phage therapy.

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

Simon Bekker-Jensen’s project investigates the potential role of the NLRP1 (Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat and Pyrin Domain Containing 1) inflammasome in combination with the upstream activator Ribotoxic Stress Response (RSR) in AD and psoriasis.

Inflammatory and hyperproliferative skin diseases, including atopic dermatitis (AD) and psoriasis, are associated with cascades of inflammatory events. A key player in innate skin immunity is the NLRP1 inflammasome, which mediates inflammation and cell death in response to a wide array of stress insults. In human keratinocytes, NLRP1 was recently shown by Simon Bekker-Jensen’s team and others to be activated by the Ribotoxic Stress Response (RSR) upon exposure to UV-B irradiation and a range of bacterial toxins.

Based on their preliminary data demonstrating that the RSR also mediates inflammation and keratinocyte hyperproliferation in vivo, the team hypothesize that these pathways have broader implications for the pathogenesis of inflammatory skin diseases.

In Simon Bekker-Jensen’s project, the validity of the RSR as a therapeutic target in the common inflammatory skin diseases psoriasis and AD will be explored. By genetic deletion and pharmacological inhibition of the RSR, the team will interrogate this pathway in several mouse models of inflammatory skin diseases. In addition, they will generate a humanized NLRP1 mouse model to study the RSR-NLRP1 signaling axis in vivo. Finally, by using 3D organotypic skin models and skin biopsies from patients, they aim to firmly establish the role of the RSR in psoriasis and AD.

The long-term goal is to leverage this insight to develop new therapeutic options for the management and treatment of inflammatory skin diseases.

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.

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.

Visit UNG:DOX’s webpage

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.

Visit Natural Science Marathon’s webpage

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

Visit the Science Olympiads’ webpage

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.