Digitalt univers til databearbejdning af citizen science-genererede forskningsdata i gymnasiet

Grantee: Marie Rathcke Lillemark, Statens Naturhistoriske Museum

Amount: DKK 1,811,250

Grant category: Education and Awareness Grants

Year: 2024

Geography: Denmark

Astronomi og naturvidenskab i børnehøjde

Grantee: Mille Marta Andersen, Go Zebra

Amount: DKK 978,420

Grant category: Education and Awareness Grants

Year: 2024

Geography: Denmark

Sustaining the Voice of Science: Increase the Impact of STEM Communication Activities at DTU Skylab

Grantee: Christian Daniel Koldbech, DTU Skylab

Amount: DKK 998,333

Grant category: Education and Awareness Grants

Year: 2024

Geography: Denmark

Hudlægens bord

Grantee: Vibeke Hjortlund, Videnskab.dk

Amount: DKK 1,262,415

Grant category: Education and Awareness Grants

Year: 2024

Geography: Denmark

Structural dissection and dynamic insights into the molecular switch of mast cells and basophils: a blueprint for novel urticaria therapies

Grantee: Rosaria Gandini, Assistant Professor, Aarhus University

Amount: DKK 3,462,144

Grant category: Research Grants in open competition

Year: 2024

Geography: Denmark

Protein stability and misfolding in keratin disorders

Grantee: Rasmus Hartmann-Petersen, Professor, University of Copenhagen

Amount: DKK 2,600,678

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.

Architecture of the Herpes simplex replication machinery and its inhibitors

Grantee: Eva Kummer, Associate Professor, Copenhagen University

Amount: DKK 4,902,307

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.

Targeted and localized skin inflammation as a potential immunotherapy against cancer

Grantee: Vasileios Bekiaris, Associate Professor, Technical University of Denmark

Amount: DKK 3,987,557

Grant category: Serendipity Grants

Year: 2023

Geography: Denmark

Vasileios Bekiaris will investigate how an observed adverse impact of a drug candidate in psoriasis may be converted to a potential treatment of cancer.

Vasileios Bekiaris and his team have been studying the mechanisms by which psoriasis is induced for several years, and their goal was to find ways to suppress it. They have discovered a molecule that is necessary for the generation and function of the immune cells responsible for causing psoriasis. Moreover, they have access to a drug that targets and neutralizes this molecule, and therefore they thought that it could potentially inhibit psoriasis. Contrary to what they expected, the drug induced inflammation and exacerbated psoriasis instead of treating it. It is known that for many cancers, inflammation promotes favourable protective immunity and helps the efficacy of immunotherapy. Using a mouse melanoma model, Vasileios Bekiaris and his team have managed to generate data suggesting that the pro-inflammatory drug could in fact suppress tumour growth.

Vasileios Bekiaris will therefore investigate the drug’s potential in cancer treatment and, if successful, may open possibilities for a new immunotherapy against skin cancers. Vasileios Bekiaris and his team also believe that this data will continue their contribution towards understanding how skin inflammation is mediated.

An unexpected link between age-associated B cells and CD8 T cells

Grantee: Søren Degn, Associate Professor, Aarhus University

Amount: DKK 3,337,538

Grant category: Serendipity Grants

Year: 2023

Geography: Denmark

Søren Degn will investigate a novel link between age-related B cells (ABCs) and cytotoxic CD8+ T cells.

Søren Degn and his team have discovered a new and unexpected link between a type of immune cells that normally produce antibodies (B cells) and a type of immune cells that are responsible for eliminating the body’s own cells when they are infected or become cancerous (CD8+ T cells). Their preliminary findings indicate that this link may play an important role when the immune system is erroneously activated, when an infection cannot be cleared, or when a cancer is established. It is not known which exact signals are responsible for the communication between these two cell types, and whether it occurs directly or via a third-party messenger. However, it is known that it occurs in the spleen, an important immune organ, which filters the blood and prevents infections, but also plays a critical role in autoimmune diseases.

The intention of Søren Degn is to understand the cellular and molecular mechanisms behind this novel link. An increased understanding may enable new therapeutic strategies in the future across a range of important diseases such as inflammatory skin disorders, autoimmune diseases, and cancer.

Dr Abildgaard Fellowship 2023

Grantee: Dr. Terkild Brink Buus, Assistant Professor, University of Copenhagen, LEO Foundation Skin Immunology Research Center

Amount: DKK 12,000,000

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.