Astronomy and natural science for kids (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
Go Zebra, a non-profit organization dedicated to stimulating children’s curiosity and bridging it to problem-solving and societal challenges through educational material with a special focus on engineering and innovation, joins forces with astrophysicist and science communicator Tina Ibsen in developing a free educational course on astronomy aimed for 4th-grade teachers and pupils. The developed material will become available for free on MeeBook (the learning platform most widely used by Danish schools), and classes participating in the project will have workshops facilitated by Go Zebra at their schools.
The overall ambition is to instill confidence in children that they can understand the world and have the capabilities to solve problems.
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
DTU Skylab will produce two video series, in total ten videos, to promote interest in STEM innovation and entrepreneurship. One of the series will consist of documentaries presenting the most significant innovations that have been realized within the DTU Skylab framework. The other series will consist of interviews with in-house experts and Skylab-based student entrepreneurs sharing their experiences and advice for students.
The videos will provide behind-the-scenes insights into the nature of scientific and technological innovation and entrepreneurship.
The dermatologist’s table (Hudlægens bord)
Grantee: Vibeke Hjortlund, Videnskab.dk
Amount: DKK 1,262,415
Grant category: Education and Awareness Grants
Year: 2024
Geography: Denmark
Videnskab.dk will produce a podcast series of 12 episodes that disseminate science-based knowledge to the public, about skin health and skin/venereal diseases. The series will be hosted by an MD in dermatology and will address several topics selected by a medical panel to reflect frequently asked questions from patients. Each episode will introduce novel research within the field with potential for enabling new or improved treatment, facilitated by Danish researchers. The podcasts are supplemented with popular science articles and short videos.
Enabling topical drug delivery of biologics across skin
Grantee: Niclas Roxhed, Associate Professor, KTH Royal Institute of Technology
Amount: DKK 4,031,088
Grant category: Research Grants in open competition
Year: 2024
Geography: Sweden
Niclas Roxhed’s technology-focused project aims to investigate the potential of spiked microspheres as vehicles for large-molecular drug delivery into skin to treat diseases.
Modern biologic drugs have transformed the way we treat many diseases. However, these drug molecules are too large to pass biologic barriers and therefore need to be injected. For skin diseases, the outermost skin layer effectively prevents larger molecules from entering the skin.
To address this problem, Niclas Roxhed and his team have tailor-made ultra-sharp spiked microspheres that painlessly penetrate only the outermost skin layer and allow delivery of large molecules into skin. In this project, they will use these spiked microspheres in an atopic dermatitis model to topically deliver large-molecular nucleic acids and nanocarriers to inhibit inflammatory reactions. To verify effective delivery, Niclas Roxhed and his team will quantify inflammatory markers in skin using micro-sampling and proteomics profiling.
The results could form the basis for highly effective delivery of biopharmaceuticals as topical creams and potentially revolutionize treatment strategies in skin disease.
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
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.
Deciphering the cellular and molecular role of mitophagy in wound healing
Grantee: Jakob Wikstrom, Associate Professor, Karolinska Institutet
Amount: DKK 4,302,900
Grant category: Research Grants in open competition
Year: 2024
Geography: Sweden
Jakob Wikstrom’s project aims to improve the understanding of mitophagy, a process where damaged and aged mitochondria are removed and recycled intracellularly, in relation to wound healing.
In the event of abnormal wound healing, chronic wounds may form and thereby place a large burden on healthcare systems. Importantly, treatment options remain limited owing to the complex nature of chronic wound pathogenesis, meaning alternative avenues need to be explored in the quest to develop novel therapies.
One avenue that Jakob Wikstrom and his team aim to pursue is that of targeting mitochondria and in particular, the quality-control process of mitophagy. Mitochondria play vital roles required for efficient wound healing, most notably in regulating metabolism. However, the role of mitophagy in wound healing is poorly understood, and only a few studies have studied it in human tissue.
Interestingly, preliminary data from human tissue and primary human cell culture for this project shows that mitophagy plays an important role in the early- and mid-wound healing stages, and that mitophagy induction aids in fibroblast and keratinocyte migration. However, the precise mechanisms of how mitophagy is required in these cell types during wound healing is yet to be elucidated.
Jakob Wikstrom and his team aim to evaluate the mechanistic role of mitophagy in wound healing through a variety of experiments on relevant human cell types, investigating metabolism, chronic inflammation, and gene expression, as well as comprehensively disseminating the impact of mitophagy on wound healing in mouse models.
Successful implementation of this project could provide novel ideas for and facilitate the development of future mitochondria-targeted wound treatments.
Epigenetic regulation of sebaceous gland development and homeostasis
Grantee: Brian Capell, Assistant Professor, University of Pennsylvania
Amount: DKK 2,885,457
Grant category: Research Grants in open competition
Year: 2024
Geography: USA
Brian Capell’s project seeks to better understand how epigenetic changes (modifications that do not change the sequence of genomic DNA) regulate the development of sebaceous glands.
Dysfunction of sebaceous glands (SGs) has been linked to a variety of common skin disorders ranging from atopic dermatitis to acne, sebaceous hyperplasia, seborrheic dermatitis and sebaceous tumors.
Brian Capell and his team have recently discovered that through genetic modification of the epigenome, they could promote a dramatic increase in the number and size of SGs (Ko, et al. Developmental Cell. In press. 2024). This surprising result demonstrated the direct role that epigenetics and chromatin organization plays in controlling SG development and abundance. It also suggested that targeting the epigenome might offer new ways to treat disorders characterized by aberrant SG development and activity.
Diseases related to aberrant SG development or activity can have a deleterious effect on both human physical and mental health. Despite this, very little is known of the role of epigenetics in SG development and homeostasis. To address this, Brian Capell’s project aims to test the influence of epigenomic modifiers and modifications upon SG development and disease to further dissect their contribution to the pathogenesis of these very common conditions.
Collectively, this project will address outstanding questions regarding the role of the epigenome in SG development and homeostasis and in common diseases driven by SG dysfunction – diseases that are both understudied and in need of better therapies.
Single-cell ribosome profiling to monitor the translational landscape in skin wound healing
Grantee: Ataman Sendoel, Assistant Professor, University of Zurich
Amount: DKK 3,979,800
Grant category: Research Grants in open competition
Year: 2024
Geography: Switzerland
Ataman Sendoel’s project seeks to improve our understanding of how genes are translated to protein during wound healing and clarify the potential of the involved pathways as drug targets.
Impaired wound healing poses a substantial medical challenge, particularly among the elderly. Understanding the gene expression changes during wound repair is therefore essential for devising new strategies to enhance wound healing in aging and disease.
While transcriptional (i.e., going from DNA to messenger-RNA) control has been extensively studied in the skin, recent studies have indicated that cellular behavior is strongly coupled to the regulation of translation (i.e., going from messenger-RNA to protein). However, how translation is controlled during wound repair and how its deregulation mechanistically contributes to impaired wound repair in aging remains unknown.
In this project, Ataman Sendoel and his team will exploit an in vivo strategy to comprehensively map the function of the translational landscape in skin wound healing. Leveraging a single-cell ribosome (an intracellular protein complex that translates messenger-RNA to protein) profiling strategy in vivo, the team will monitor skin cells during different wound healing stages. By coupling this with single-cell RNA sequencing, they will determine cell-type-specific translational efficiencies and identify factors relevant to wound repair in aging.
Finally, Ataman Sendoel and his team aim to carry out a mini-screen to identify FDA-approved drugs that selectively increase the translational efficiency of skin wound repair factors.
Collectively, these data will provide systematic insights into the translational landscape of skin wound repair, and how deregulated translation leads to impaired wound repair. It may also clarify if protein synthesis pathways could be targeted therapeutically to restore wound healing.
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.