Exploring the serendipitous connection between a mitochondria fission protein and melanosomes maturation

Grantee: Marta Giacomello, Associate Professor, University of Padua

Amount: DKK 3,885,368

Grant category: Serendipity Grants

Year: 2023

Geography: Italy

Marta Giacomello aims to elucidate the role of a newly discovered mitochondrial fission protein in organelle maturation by exploring its impact on melanosome development and lipid droplet formation.

Melanogenesis, the process of synthesis and storage of the pigment responsible for skin color, melanin, occurs at specialized cell organelles named melanosomes. The mechanisms underlying melanin synthesis are not fully understood, but recent data suggest that mitochondrial physiology influences melanogenesis. Marta Giacomello and her team discovered that a mitochondrial fission factor, serendipitously found at the melanosome-mitochondria interface, controls the size of early melanosomes and melanin levels independently of its role in mitochondrial morphology.

The team aims to demonstrate that the identified mitochondria fission factor is a common regulator of organelle maturation, which exerts its specific effect based on its subcellular localization and interaction partners. They will first investigate its role in melanosome maturation, and then to generalize its function by extending the analysis to lipid droplets.

By elucidating how the identified fission factor switches from its mitochondrial to its melanosomal function, Marta Giacomello may generate milestone findings in the field of melanogenesis, and proof-of-concept evidence for its general role as a master regulator of organelles’ fission and maturation. Potentially, the results of this project could lead to breakthroughs in the fundamental understanding of cell biology.

Switching on melanogenesis: characterization of a yet undiscovered player in melanin production

Grantee: Marta Giacomello, Assistant Professor, University of Padua

Amount: DKK 3,990,000

Grant category: Research Grants in open competition

Year: 2020

Geography: Italy

The aim of this project is to further investigate the pathways leading to the production of melanin, a biological molecule that determines skin pigmentation and is responsible for skin color. The complex process for melanin biosynthesis, named melanogenesis, is not yet fully understood. Dysfunctional production of melanin reduces the protection of the skin from ultraviolet light and causes severe dermatological conditions like albinism and vitiligo.   

In preliminary studies, Marta Giacomello has found that the pro-apoptotic protein AIFM3 is likely to be pivotal for melanogenesis. AIFM3 controls the crosstalk among two cell structures: the ‘endoplasmic reticulum’ (important in the synthesis, folding, modification, and transport of proteins), and ‘mitochondria’ (the ‘motors’ that generate most of the chemical energy needed to power the cell’s biochemical reactions).   

Marta Giacomello’s research group will investigate this protein by analyzing its structure and function, its role in intracellular signaling cascades, its physical positioning within the cell and its role in melanogenesis.  

As AIFM3 is very poorly studied (~10 publications), the project will provide unprecedented insight into its role in determining skin pigmentation. 

Influence of microbes on development of skin diseases

Grantee: Anders Johannes Hansen, PhD, Associate Professor, University of Copenhagen, Denmark, Robert Gniadecki, MD, Professor, Dermatology Department, Bispebjerg Hospital, Copenhagen, Denmark, Kim Holmstrøm, R&D Manager, Department of Biomedical Technology, Bioneer A/S, and Nicola Segata, PhD, Assistant Professor and Principal Investigator, Computational Metagenomics, CIBIO, University of Trento, Italy

Amount: DKK 5,035,000

Grant category: Research Grants in open competition

Year: 2016

Geography: Denmark, Italy

By combining new data from the human skin microbiome with existing knowledge of pathophysiology and clinical phenotypes of Atopic Dermatitis, AD, Actinic Keratosis, AK and non-melanoma skin cancer, the team will seek to establish a novel understanding of these diseases.

Recent microbiome analyses have revealed that mammalian body surfaces are colonized by vast numbers of bacterial communities, which motivates the exploration of the role of the microbiota in normal and diseased skin. There are indications that the skin microbiome plays a key role in both inflammatory skin disease and non-melanoma skin cancer.

The vision for the team’s research endeavours is to explore the microbiome for the identification of new targets for treatment, and for the development of improved treatment modalities for patients with AD, AK and non-melanoma skin cancer.

The team’s explorations will potentially also lead to the development of better and more specific and sensitive diagnostic and prognostic methods for monitoring skin disease.

The Danish-Italian team will work from a unique microbiome discovery platform established at the University of Copenhagen (UCPH) within the GenomeDenmark Cancer & Pathogen project. The platform utilizes procedures enriching various types of microbes combined with state of the art DNA and RNA sequencing and bioinformatics data analysis.

The LEO Foundation Award 2015 – Gold Award

Grantee: Dr. Nicola Segata

Amount: DKK 1,000,000

Grant category: LEO Foundation Awards

Year: 2015

Geography: Italy

Presented to Dr. Nicola Segata, Assistant Professor and Principal Investigator, Laboratory of Computational Metagenomics, Centre for Integrative Biology, University of Trento, Italy.

Dr. Segata has pioneered novel advanced techniques for the characterisation of the microorganisms colonising the human body (the microbiome). His discoveries have proven to be crucial in studying microbial communities and unravelling the structure of the human skin microbiome. The characterisation of the microbiome is a fast-growing research field because it plays an important role in many pathological conditions, including skin diseases such as atopic dermatitis, acne, psoriasis and rosacea.

The LEO Foundation Award 2012 – Silver Award

Grantee: Dr. Andrea Chiricozzi

Amount: DKK 500,000

Grant category: LEO Foundation Awards

Year: 2012

Geography: Italy

Presented to skin immunology specialist Dr. Andrea Chiricozzi at the Department of Dermatology, University of Rome Tor Vergata, Italy.

Chiricozzi’s research focuses on chronic skin inflammation and the pathogenic circuits underlying the formation of skin lesions, particularly in regard to psoriasis and atopic dermatitis. The award will support Chiricozzi’s on-going research into the pathogenic mechanisms in skin disorders and novel therapeutic strategies.