Grant geography: Denmark

Grant category: Research Grants in open competition

Year: 2022

Geography: Denmark

This project led by Lotte K. Vogel aims to elucidate the role of the protease matriptase (an enzyme that cleaves proteins) in a variant of Ichthyosis, a common skin disease that causes “fish-scale” like skin with poor treatment options.

The molecular mechanisms behind ichthyosis are not understood, but variations in several genes may cause ichthyosis. Variants of the ST14 gene, which encodes the serine protease matriptase, lead to a type of ichthyosis called Autosomal Recessive Congenital Ichthyosis 11 (ARCI11). The prevalence of ARCI11 is elusive at present.

Lotte and her team’s preliminary data show that ARCI11-related matriptase variants are unable to activate a certain substrate (a protease on its own), suggesting that ARCI11 is caused by a lack of activation of this protease. Results from the group also suggest that inactivation of a certain enzyme cascade leads to Ichthyosis. Surprisingly, for several enzymes in this cascade both the zymogen form and the activated form of the enzyme exhibit proteolytic activity.

In this project, Lotte aims to investigate the importance of matriptase in ARCI11 through a three-pronged approach: (1) by elucidating whether a protease located downstream of matriptase in the same pathway can be activated by an appropriate soluble enzyme which is suitable for topical application to the skin. (2) by elucidating whether ARCI11 is caused by a difference in substrate preferences between the zymogen form and the activated form of these enzymes and (3) by systematically screening for genetic variants of matriptase causing ARCI11 and estimating their frequency in the population. The genetic material to do a more systematic search for ARCI11-causing variants of matriptase and estimate their frequency Is already available.

If successful, Lotte’s project will make a solid and original contribution to the understanding of ichthyosis that may lead to improved treatment options.

Grant category: Research Grants in open competition

Year: 2022

Geography: Denmark

Gregers Andersen’s project aims to understand the role of disease-related mutations of a central inflammation-regulating protein on immune cells in systemic lupus erythematosus (SLE).

Systemic lupus erythematosus is a severe autoimmune disease in which our immune system is erroneously activated. This leads to inflammation that may destroy tissue, such as the kidney. SLE often manifests itself with visible skin rashes that are difficult to treat and debilitating for the patient. Current options for treatment of SLE are insufficient and still rely heavily on steroids as the mainstay of treatment.

Both environmental and genetic factors contribute to SLE pathogenesis. The strongest association between SLE and the information encoded in our genetic material is observed for a specific mutation in a gene called ITGAM. This gene codes for a protein called αMβ2 located at the surface of our immune cells. When the αMβ2 protein recognizes specific proteins on other cells, the immune cell contributes to dampening inflammation. When the ITGAM gene is mutated, the immune cells are less efficient in suppressing inflammation.

Using the most powerful microscope available, Gregers’ research project will investigate in atomic detail how the mutation interferes with the normal function of the αMβ2 protein. Furthermore, the effects of a new antibody capable of increasing the activity of αMβ2 will be exhaustively investigated. Experiments comparing the effects of this antibody on immune cells from healthy and SLE individuals will be central in deciding whether the antibody is a candidate for a new type of therapeutic agent.

Grant category: Education and Awareness Grants

Year: 2022

Geography: Denmark

The Bloom Festival is celebrated annually and places a focus on acknowledging the wonders of nature and science – the festival is held each year in Søndermarken on Frederiksberg. The festival has existed since 2017, with the LEO Foundation offering funding support since 2019.  

The festival is organized by ADBC, which has success in running other alike initiatives, such as the annual Golden Days festival. The annual Bloom Festival is a contribution to strengthening the landscape of STEM-initiatives in Denmark, and functions as an innovative event which aims to enlighten us on the universe, the world, and ourselves. 

By uniting the best from the worlds of festivals and science, Bloom aims to tackle Life’s greatest questions through debates, talks, laboratories, conversations, and nature walks. 

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Grant category: Standalone grants

Year: 2022

Geography: Denmark

The Institute for Immunology and Microbiology is the host of the LEO Foundation’s major strategic initiative, the LEO Foundation Skin Immunology Center (SIC). ISIM has been established with flow cytometry and single cell sequencing as main areas of expertise and serves as a platform for integrative cell analysis.  

ISIM provides local and external research groups and biotech companies with access to highly specialized equipment for analysis using flow cytometry and state-of-the-art single cell sequencing, as well as highly specialized staff who are experts at analyzing samples in complex projects.  

In support of ISIM the LEO Foundation provides new equipment to the organization to upgrade technological options for cell and single cell analysis, to make it possible to implement new methods using new and existing equipment together, and to help ensure that the core facility can support experiments in the entirety of their pipeline – from initial idea formation to full-scale experiments.  

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Grant category: Standalone grants

Year: 2022

Geography: Denmark

SIC Springtime School is hosted annually by the LEO Foundation Skim Immunology Research Center (SIC) and has shown to be a great success over the two previous years. The international school is held at Hornbækhus on the North Coast of Zealand and forms part of SIC’s educational and career development activities – in 2022 representing 86 speakers, international students, and postdoc participants.  

The SIC Springtime School offers participants the opportunity to interact with leading scientists, providing for rich and positive learning experiences.  

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Grant category: Standalone grants

Year: 2022

Geography: Denmark

The SIC PhD Program aims to nurture the development of upcoming skin immunologists and to further tap into the collaborative possibilities of the research groups within the by the LEO Foundation Skim Immunology Research Center (SIC). 

The program features a 1+3-year structure for five PhD studies at the center. In their first year, students are onboarded into the program as Research Assistants, before eventually enrolling as full-time PhD students in their year two. 

The program sets to strengthen not only the collaborative nature of the center, but also allows for potentially high-gain projects to be set into motion. 

Grant category: Education and Awareness Grants

Year: 2022

Geography: Denmark

Astra has existed as an organization since 2015-2017 and was born out of a merger between Danish Science Factory, ‘Science Talenter’ and the publicly funded NTS-center (Det Nationale Center for Undervisning i Natur, Teknik og Sundhed). Astra defines its mission as to bring together relevant actors to progress and expand upon the quality and framing of the education of the natural sciences. 

The LEO Foundation has previously supported numerous of Astra’s initiatives and activities, and with this grant, funding is dispersed between 3 of Astra’s largest programs: ‘Unge Forskere‘ (Young Scientists) an annual research-idea and talent competition for children and youths in elementary- and high -school with a passion for science and technology, ‘Big Bang‘ an annual science conference for professionals within teaching and communication of STEM and science topics, and ‘Science Talenter’ (Science Talents) which organizes science camps for the oldest pupils from elementary school as well as A-level students with a special interest in and talent for STEM-topics. 

Grant category: Education and Awareness Grants

Year: 2022

Geography: Denmark

Lex.dk is an association formed by the Danish Universities, Gyldendal A/S, G.E.C. Gad’s Foundation and the Danish Society for Language and Literature, which was originally established around the online version of ‘Den Store Danske’, Gyldendal’s well-renowned encyclopedia. The encyclopedia focuses on nature, culture, science, and society with a national point of departure and a global outlook.  

Lex.dk has become the go-to resource for dissemination of validated research information from many areas of expertise and is written by researchers and experts. The encyclopedia serves as an important source to the broader public, but rather importantly, also to pupils in elementary school and A-level students when compiling information for assignments and reports.  

Lex.dk is unique in that there is no other encyclopedia source in Danish that provides a broad perspective on health and health sciences through focused articles. This grant supports updating and significantly expanding content on health and health research through collaboration with the Norwegian counterpart. This means that newly revised and well-researched information on will become available to the general Danish public online. 

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Grant category: Research Grants in open competition

Year: 2022

Geography: Denmark

Claus Johansen’s project investigates the role of the protein ERAP2 in the pathogenesis of psoriasis.

Psoriasis is considered an autoimmune disease – i.e., a disease in which the T-cells of the immune system attack and destroy the body’s own cells by error. During an exposure to external factors (peptides, bacteria etc) a system of specialized cells engulfs, digests, and presents peptide fragments (antigens) of these external factors on their surface to the body’s immune cells – usually cytotoxic CD8+ T-cells – which, once activated, then surveil, identify, and destroy foreign elements containing that specific peptide or peptides with very similar overall structure. The peptides are presented by a specific receptor, called the human leukocyte antigen (HLA) receptor and it is well-known that a particular subtype of this receptor, the HLA-C receptor is dominant in psoriatic patients – still, concrete disease-specific self-antigens have not yet been identified. Recent results have indicated that a protein, ERAP2, which facilitates the association of antigen peptides to HLA receptors may have a role to play in the erroneous recognition of self-antigens in autoimmune diseases like psoriasis. Claus and his team aim to clarify the role of this protein in the current proposal.

If successful, their project may help shed further light on the autoimmune characteristics of psoriasis – and eventually help guide new treatment approaches.

Grant category: Research Grants in open competition

Year: 2022

Geography: Denmark

This project, led by Søren Degn, aims to investigate the role of a newly discovered immune cell, the T follicular regulatory cell (Tfr), in controlling systemic autoimmunity.

Søren Degn and his team have discovered that Tfrs are able to maintain tolerance in the skin even in the face of systemic inflammation, which in that case appear to be reversible, but also that if Tfr control in the skin fails, the systemic inflammation becomes irreversible and chronic.

Using a mouse model where Tfrs are selectively deleted, Søren and his team will investigate immune responses and identify which specific self-antigens are targeted when the tolerance maintained by the Tfrs is lost.