23.11.2023
Doctoral thesis on the underlying molecular mechanisms of intestinal inflammations
M.Sc. Aravind Kumar Mohan’s doctoral thesis in Cell biology will be put forth for public defence at Faculty of Science and Engineering at Åbo Akademi University.
The thesis is entitled Regulation of inflammatory signalling by caspases and M1-linked ubiquitin chains in Drosophila melanogaster.
The public defence of the doctoral thesis takes place on 30 November 2023 at 1PM in the auditorium Arje Scheini, Dentalia (University of Turku), Lemminkäisenkatu 2, Turku. Professor Seamus Martin, Trinity College Dublin, Ireland will serve as opponent and Senior University Lecturer, Annika Meinander, Åbo Akademi University, as custos.
Summary
The innate immune system is important for multicellular organisms to fight against pathogens. The NF-κB signaling pathway is a major regulator of innate immune responses. The NF-κB activity needs to be tightly regulated as their inactivation leads to immune deficiency and overactivation leads to inflammatory diseases and can even promote cancer. In order to treat inflammatory diseases, we need to understand the underlying molecular mechanisms behind disease conditions. This thesis describes the role of caspases and ubiquitin chains in regulating the NF-κB pathway.
The intestine is an environment where both the commensal and pathogenic bacteria come into contact with the host. While the immune system must respond to pathogenic bacteria, it is also important to tolerate beneficial commensal bacteria to avoid unwanted inflammation. As determination of the molecular mechanisms of intestinal inflammation is challenging to study in mammalian systems, we have used Drosophila melanogaster, commonly known as the fruit fly, as a model organism. As the fly’s intestine is similar in structure and function to humans, and the signalling mechanisms that regulate inflammation are similar, this is a convenient and relevant model to study inflammation in the intestine.
The results from this doctoral research shows that two proteolytic caspase enzymes called Drice and Dredd regulate NF-κB activation by controlling the stability of signalling proteins. Drice is involved in degradation of NF-κB activating proteins as it is important to prohibit beneficial commensal bacteria from inducing inflammation. In contrast, Dredd is required for stabilisation of NF-κB-inducers. As caspases are mainly known for their functions as inducers of cell death, this thesis describes novel non-apoptotic roles of caspases. In addition, the thesis describes how ubiquitination controls the activity of Drice and Dredd. Thereby, the thesis brings in fundamental knowledge about the molecular regulation of the signalling pathways that control inflammation in the intestine.
The PhD candidate is affiliated with the InFLAMES research flagship. InFLAMES Flagship is a joint initiative of University of Turku and Åbo Akademi University. The goal of the Flagship is to integrate the immunological and immunology-related research activities to develop and exploit new diagnostic and therapeutic tools for personalised medicine.
Aravind Kumar Mohan was born in 1987 in Madurai, India. He can be reached by email aravind.mohan@abo.fi.
The doctoral thesis can be read online through the Doria publication archive.