In 2021, the first productive attempt at functionally describing an abundant protein in human plasma was published. The proposed function was inhibition of an arm of the human immune system denoted the complement cascade, and the protein was called inter-α-trypsin inhibitor heavy chain 4 – in short, ITIH4. With a sound suggestion for what ITIH4 does in our body, the question of how it does so only became more enticing. Thus, the foundation was laid for Martin Høgholm Jørgensen’s PhD studies.

By mixing the complement protease whose activity is inhibited with ITIH4 and imaging their combination using cryogenic electron microscopy, the dramatic rearrangements following the action of ITIH4 were observed and provided the first model of its unique inhibition mechanism. Considering the abundance of ITIH4, these first mechanistic insights into its structure and function provide an essential model to understand its relevance to our health and potentially hack its role therapeutically in case of disease.

The PhD study was completed at Department of Molecular Biology and Genetics, Faculty of Natural Sciences, Aarhus University.

This summary was prepared by the PhD student.

Time: Wednesday, 12 November 2025 at 12:15
Place: Building 1253, room 211, Merete Barker, Lake Auditoriums, Aarhus University, Bartholins Allé 3, 8000 Aarhus C.
Title of PhD thesis: Microscopic Leaps in Complement Comprehension
Contact information: Martin Høgholm Jørgensen, e-mail: mhj@mbg.au.dk, tel.: +45 30586315
Members of the assessment committee:
Professor Christoph Schmidt, Department of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, University of Ulm Medical Centre, Germany
Associate Professor Nicholas M. I. Taylor, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Denmark
Senior researcher Jan Trige Rasmussen (chair), Department of Molecular Biology and Genetics, Aarhus University, Denmark
Main supervisor: Professor Gregers Rom Andersen, Department of Molecular Biology and Genetics, Aarhus University, Denmark
Language: The PhD dissertation will be defended in English

The defence is public.
The PhD thesis is available for reading at the Graduate School of Natural Sciences/GSNS, Ny Munkegade 120, building 1521, 8000 Aarhus C