Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

Drosophila embryonic macrophages as a model system for studying migration and bacterial infection in real time.

In plain English

AI plain-English summary

Fruit fly embryos will be used to watch immune cells move, chase bacteria, and engulf them in real time under a microscope. This matters because human immune cells rely on the same basic mechanisms to crawl toward infections and clear them. When those mechanisms fail, people become vulnerable to persistent infections or chronic inflammation. The researchers will systematically switch off individual genes across the fly genome to identify which ones control cell migration, wound-seeking behaviour, and bacterial clearance. They will also analyse which genes are active in different immune cell populations as the embryo develops. If successful, this work will produce a catalogue of genes required for immune cells to navigate tissues and destroy bacteria. Because the core machinery of cell movement is shared across animals, the genes discovered in flies are strong candidates for study in human immune disorders. This is fundamental science—there is no immediate medical application—but similar work in flies has previously revealed the genetic basis of innate immunity, a discovery that later informed treatments for sepsis and autoimmune disease.

View original technical description
We will use Drosophila embryonic hemocytes as a model to study cell migration and chemotaxis in vivo. We will initially investigate the dynamic interplay between microtubules and actin in migratory cells as well as further investigating the role of microtubules during contact inhibition and in the maintanence of polarity in hemocytes. In addition to elucidating their cytoskeletal regulation we will explore what external cues direct hemocyte migrations and how their contact inhibitory behaviour is regulated. To this end we will carry out a genome wide-RNAi screen allowing us to identify novel genes required for normal hemocyte dispersal during development as well as their rapid chemotaxis towards epithelial wounds. In addition we will carry out a microarray approach to probe the transcriptome of discrete populations of hemocytes at different developmental timepoints in order to understand the process of hemocyte maturation and specification during development. Finally we also plan t o continue our initial studies using Drosophila embryos as a model system for following bacterial infection in real time. We will test the in vivo function of genes previously identified in RNAi screens in vitro as being important for the recognition, engulfment and degradation of bacteria by S2 cells in culture.

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Researchers

Will Wood (EPMC Awardee)

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Original classification

Senior Research Fellowship Basic

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