Explore our grantees and awardees

Grant category: Research Grants in open competition

Year: 2024

Geography: Denmark

Rosaria Gandini’s project investigates the molecular details of the IgE-FceRI complex and its functioning on mast cells and basophils in order to improve treatment opportunities for urticaria.

Urticaria, a common inflammatory skin disorder characterized by itchy wheals, angioedema, or both, manifests in acute (AU) and chronic (CU) forms. It significantly impairs patients’ quality of life, causing sleep disturbances due to pruritus, fatigue, and anxiety. The symptoms arise from the activation of skin mast cells and basophils, leading to the release of histamine and other inflammatory mediators. This activation is initiated by cross-linking and clustering of the complexes between immunoglobulin E (IgE) and its high-affinity receptor, FceRI, which is expressed on the surface of these cells.

The FceRI-IgE complex hence acts as a powerful molecular switch, which initiates the inflammatory cascade and thus provides an attractive target for drug intervention. The structural basis of this activity, however, remains open.

Rosaria Gandini’s project aims to determine the structure of the FceRI-IgE membrane complex using state of the art Cryo Electron Microscopy (cryo-EM).

Successful elucidation of the molecular details of the entire complex and its conformations will allow identification of specific regions on FceRI for targeted intervention. This knowledge will deepen the understanding of the interaction of antibodies with Fc receptors in general and may pave the way for the development of specific and effective treatment of urticaria and related disorders.

Grant category: Research Grants in open competition

Year: 2024

Geography: Denmark

Rasmus Hartmann-Petersen’s project aims to characterize all possible missense variants (changes in genes which introduce a different amino acid in the resulting protein) in human keratins and investigate the importance of these variants in associated diseases.

Keratins are intermediate filament proteins that form a cytoskeletal network within cells. They are expressed in a tissue-specific fashion and form heterodimers, which then further oligomerize into filaments. Variants in several keratin encoding genes are linked to a range of hereditary disorders, including several epidermal skin diseases. On the molecular level, some pathogenic keratin variants appear to cause aggregation of the keratins.

In Rasmus Hartmann-Petersen’s project it is hypothesized that most keratin-disorders are protein misfolding diseases, i.e. diseases where the underlying genetic variants cause misfolding of the encoding protein. Rasmus and his team aim to explore this hypothesis by using computational tools, including large language models (a specific form of AI). They will test the validity of the computational predictions through focused cellular studies on selected keratins and identify components regulating keratin turnover.

The results will highlight the underlying molecular mechanisms for keratin-linked human disorders and provide predictions on the severity of all possible (both known and yet unobserved) coding variants in human keratin genes. The results could be of diagnostic value, but may also highlight the cellular protein folding and protein quality control machinery as potential therapeutic targets.

Grant category: Research Grants in open competition

Year: 2024

Geography: Denmark

Eva Kummer’s project targets to improve our understanding of the replication machinery of the skin-infecting herpes simplex virus (HSV) in order to improve and expand treatment opportunities.

HSV is one of the most widespread viral infections. The virus persists lifelong in the nerve system of the host and causes recurrent infections with mild to severe symptoms.

Since decades, treatment of herpes infections has exclusively targeted the viral replicative DNA polymerase (an enzyme that copies the viral DNA) using nucleoside analogs. However, resistance to current nucleoside analogs is emerging necessitating the search for alternative targets.

A major caveat in developing anti-herpetic compounds is a lack of structural information of other components of the herpes simplex replication system, which are likely strong candidates for targeted drug development. Eva Kummer and her team will use cryo-electron microscopy to visualize the architecture and working principles of the protein complexes that drive herpes simplex replication. They will also aim to clarify how novel anti-herpetic drugs block the viral replication machinery and why naturally occurring resistance mutations inhibit their action.

Overall, the project will generate structural and functional insights of the HSV replication strategy and potentially improve and accelerate anti-viral drug design.

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: 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.

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.

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

Jes Dietrich’s project aims to develop a vaccine against a common pathogenic bacterium.

Streptococcus Pyogenes (Group A streptococcus, GAS) is a human pathogen causing billions of infections each year throughout the world. GAS is one of the most important bacterial causes of skin and soft tissue infections worldwide. There is no vaccine against GAS and the optimal immunity to protect the skin against GAS infection is still not fully known.

Jes Dietrich and his team have recently characterized the recognition of all GAS proteins in previously infected human adults and children, and successfully identified several GAS antigens that showed protective potential against a GAS skin infection.

Here, they will follow up on these discoveries. The aim is to produce a vaccine hybrid construct that will target several antigens on the bacterial surface as well as several of the bacterium’s early key immune inhibiting functions. Moreover, they will also investigate the immune correlates of skin protection.

Thus, the goal for this project is to develop a vaccine that protects against a GAS skin infection, and which is ready to proceed towards future clinical trials.

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

This project of Ulrich auf dem Keller aims to elucidate the potential role of a set of recently discovered proteins in atopic dermatitis that may contribute to disease development.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects people of all ages. It is one of the most common skin diseases, affecting approximately 10-20% of children and 1-3% of adults worldwide. AD can be a frustrating and uncomfortable condition that can significantly impact a person’s quality of life.

Despite extensive research it is not fully clear, if AD is primarily caused by a defect barrier function of the skin, allowing uncontrolled entry of environmental allergens that trigger an immune response, or by immunological disorders that in turn weaken the skin’s protective barrier, exaggerating the disease in a vicious cycle. Most likely, both contribute to predisposition and development of AD, but there are differences between patients which call for customized therapies.

Together with basic skin researchers in Switzerland and dermatologists in Germany, Ulrich auf dem Keller has identified proteins in non-lesional skin of AD patients whose activities might impair skin barrier integrity mostly independent of an immune response. This project will use human skin models and advanced protein analytics to understand if and how they might exert these detrimental activities and thereby contribute to predisposition to AD in affected individuals. Moreover, they will test their findings in samples from AD patients with a long-term aim to contribute to new strategies for development of therapeutics as alternatives to frequently applied emollients in barrier repair therapy.

Grant category: Research Grants in open competition

Year: 2023

Geography: Denmark

This research project aims to synergistically improve patient treatment and improve understanding of the underlying biological and chemical mechanisms of cutaneous dystrophic calcinosis (DC) – a disease causing exaggerated deposition of calcium salts in skin.

These pathological calcifications cause severe ulcerations and pain in patients with systemic sclerosis (SSc) and negatively impact their quality of life. Today, reliable methods of quantifying the distribution, volume and composition of calcium crystal deposits are lacking.

Combining the expertise of data scientists and molecular biologists with medical experts in the field of radiology, dermatology, and rheumatology, Mette Mogensen and her team will create a new approach for quantifying calcium crystal deposits in skin and soft tissue in patients suffering from SSc, which is highly needed to monitor disease progression and potential treatment effects in future clinical trials. Several smaller studies have shown a potential for treating DC using sodium thiosulphate (STS). The aim of this study is to explore the characteristics of DC and investigate how STS treatment effects can be monitored over time with novel biomarkers (from blood and skin biopsies) and by advanced imaging technologies.

The vision is to cure calcinosis and the goal of this project is to increase quality of life for patients by development of an effective, targeted treatment that may offer therapeutic potential to all DC patients globally.