Structure and modulation of the integrin receptor αMβ2 in relation to SLE

Grantee: Gregers Andersen, Professor, Aarhus University

Amount: DKK 1,713,040

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.

Bloom Festival 2023-2025

Grantee: Svante Lindeburg, ABDC

Amount: DKK 1,650,000

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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New equipment for Flow Cytometry and Single Cell Sequencing

Grantee: University of Copenhagen

Amount: DKK 10,755,847

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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The SIC Springtime School 2023-2028

Grantee: University of Copenhagen

Amount: DKK 4,300,000

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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SIC PhD Program 2023-2027

Grantee: University of Copenhagen

Amount: DKK 13,387,500

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. 

Astra activities 2023-2025

Grantee: Mikkel Bohm, Astra

Amount: DKK 12,000,000

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. 

Formidling af sundhedsvidenskabelig viden på platformen lex.dk

Grantee: Lex.dk

Amount: DKK 1,000,000

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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Digging deep for filaggrin’s function in regulating epidermal barrier formation

Grantee: Ellen van den Bogaard, Professor, Radboud University Medical Center

Amount: DKK 3,929,813

Grant category: Research Grants in open competition

Year: 2022

Geography: Netherlands

The aim of Ellen’s project is to improve the understanding of the role of skin protein filaggrin (FLG) in regulating and controlling epidermal keratinocyte robustness and differentiation.

Ever since the discovery that loss-of-function mutations in the FLG gene are the main risk factor for developing Atopic Dermatitis (AD), many studies have aimed to relate the presence or absence of FLG to processes involved in skin homeostasis. The filaggrin protein is comprised of several repetitive elements as well as two unique domains, A and B. While many mutations in the filaggrin monomers are known to be important in AD, the role of the A and B domains have been less studied.

Previous investigation, featuring collaborator and postdoctoral fellow Jos P.H. Smits, discovered that mutations in these domains affect the expression of genes that are important for terminal differentiation of epidermal keratinocytes. The terminal differentiation of keratinocytes is important for the formation of the skin barrier. In this project, the team want to expand initial findings into elaborate studies using 3D skin organoids, also called “human skin equivalents” combined with in-depth molecular and functional analyses. Ellen’s group has developed many of these 3D skin equivalents to resemble both the structure and environment of real skin. By exposing the skin equivalents to relevant environmental factors, they will study how mutations in the filaggrin A and B domains affect keratinocyte differentiation and terminal fate and ultimately the overall skin barrier function. The hope is to identify potential new targets for therapeutic interventions in AD by modifying the expression of filaggrin and thereby regulating the barrier function of the skin.

Single Cell Transcriptomic Classification of Inflammatory Skin Disease

Grantee: Jeffrey Cheng, Associate Professor, The Regents of the University of California San Francisco

Amount: DKK 3,999,960

Grant category: Research Grants in open competition

Year: 2022

Geography: USA

Jeffrey Cheng’s project aims to improve our understanding and discrimination of chronic atypical skin rashes which do not fit into well-defined clinical categories. Jeffrey along with his team will approach this by first mapping gene expression variations on a single cell level for a number of prototypical rash types. This will allow them to create a framework to identify variations that can discriminate between well characterized rash types, which each have different treatment regimens. While they have already done this for rashes with atopic dermatitis- and psoriasis-like features, this project will add information about rashes with features common to cutaneous sarcoidosis and lupus erythematosus. Based on these findings, Jeffrey aims to establish a more accessible approach to classify these rashes by assessing tissue samples for presence of disease-relevant proteins.

If successful, Jeffrey and his team will provide important guidance for optimal classification and subsequent treatment of otherwise indeterminant rashes.

Deliniating the functional role of ERAP2 and HLA-C in the pathogenesis of psoriasis

Grantee: Claus Johansen, Associate Professor, Aarhus University

Amount: DKK 3,230,325

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.