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A project led by Irina Udalova and co-led by Marco Fritzsche and Erinke van Grinsven, a senior postdoctoral fellow in the Udalova laboratory, has received funding from the Biotechnology and Biological Sciences Research Council (BBSRC) to uncover why and how neutrophils experience dramatic nuclear changes during their development, and the link between maladaptive neutrophil development and chronic inflammation.

Three people are side-by-side smiling at the camera in separate pictures: Marco Fritzsche, Irina Udalova, and Erinke van Grinsven.

Neutrophils are the most abundant type of white blood cell and are crucial for defending us from pathogens, but they live for only hours or days. To keep up the defence, our bone marrow needs to produce billions of neutrophils every day through an intricate process known as granulopoiesis. 

During granulopoiesis, a progenitor cell goes through successive changes to become a mature neutrophil which is then released from the bone marrow into the bloodstream. One of the most notable changes is the transformation of the nucleus from a simple structure to a complex, segmented structure with multiple lobes.

Nobody knows how or why this shape is formed, but Kennedy researchers hope to find out. This deeper knowledge of neutrophil formation would help us understand why the release of immature, dysfunctional, and hyperactive neutrophils is linked to chronic inflammatory diseases and cancer. In turn, this knowledge could potentially be used to design neutrophil-based interventions for these life-limiting conditions.

The team, that also includes Abhinandan Deva Prasad, Ananda Mukherjee and Julia Salafranca Gomez from the Udalova laboratory, and Jacky (Ka Long) Ko and Narain Karedla from the Fritzsche laboratory, predicts that the gradual changes in nuclear shape are related to the gradual acquisition of key nuclear functionalities of the neutrophil nucleus, and will combine their skills in molecular immunology and advanced bioimaging and biomechanics to dig deep into the mechanisms of granulopoiesis. The team already developed a novel method for defining nuclear shape in live cells, aided by 3D microscopy and Artificial Intelligence (AI). They will build upon this method to elucidate, for the first time, the molecular programming of neutrophils and why and how they go through complex nuclear changes during development.

Irina Udalova said 'Our newly established collaboration and developed approaches are key to the success of this research project. This has been picked up by the reviewers who suggested that we might be the only people in the world who can carry out the proposed research. We hope to generate new standards for phenotype assignment across the neutrophil maturation trajectory, that will be useful clinically in the future.'

Speaking about the funding, Marco Fritzsche said: 'We are tremendously thankful to the BBSRC board who were very supportive of this proposal and deemed it extremely relevant to their strategy.'