The mushroom body of the fruit fly, Drosophila melanogaster, is a central brain structure essential for learning, decision making, and integration of sensory information with internal state. Kenyon cells (KCs), the principal neurons of the mushroom body, are organised into distinct subtypes and encode odour information to during olfactory memory encoding and retrieval. In both vertebrates and insects, expression of activity-regulated genes often increases in neurons that are active in response to sensory stimuli. Hr38, the fly orthologue of the mammalian Nr4a nuclear receptors, is generally considered one of the major candidate activity-regulated genes in the Drosophila brain.

Surprisingly, our preliminary data suggests that the number of Hr38-positive KCs does not change in response to odours. Instead, Hr38 expression varies with the time of day, indicating regulation via intrinsic cues instead of direct activity-dependent induction. Further, knocking down Hr38 in KCs does not impair memory formation or retrieval, suggesting that this gene is not required for olfactory memory.

The overarching goals of this project are to understand what controls Hr38 expression in KCs, and how this gene may act as an integrator of intrinsic timing cues or other internal state signals. Specifically, the student will (1) characterise the temporal and spatial distribution of Hr38-positive KCs across mushroom body subtypes; (2) perform transcriptomics comparisons of Hr38-positive and Hr38-negative KCs to identify molecular signatures that distinguish these populations; and (3) investigate how Hr38 contributes to the regulation of mushroom body circuits, using genetic tools to knock down Hr38 or block output from Hr38-positive KCs while monitoring behavioural rhythms, activity patterns, and memory formation.

Overall, this project will provide insight into the molecular and functional heterogeneity within mushroom body neurons.

Research Environment:

The work will take place in the group of Dr Vincent Croset in the Department of Biosciences at Durham University. The successful applicant will have the opportunity to work in a vibrant scientific environment and learn essential skills to prepare them for a career in research. They will learn about brain physiology, behaviour, anatomy and histology, genetics, and molecular biology. They will also acquire transferrable soft skills in oral and written scientific communication, critical scientific thinking, and good laboratory practice, including organisation, planning and the ethics of science. While prior experience in neurobiology or Drosophila work is desirable, we are primarily looking for a curious and motivated student.

Durham University

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Dynamic regulation of activity-regulated genes in the Drosophila mushroom body