A global timing mechanism regulates cell-type-specific wiring programmes.

The assembly of neural circuits is dependent on precise spatiotemporal expression of cell recognition molecules1-5. Factors controlling cell type specificity have been identified6-8, but how timing is determined remains unknown. Here we describe induction of a cascade of transcription factors by a steroid hormone (ecdysone) in all fly visual system neurons spanning target recognition and synaptogenesis. We demonstrate through single-cell sequencing that the ecdysone pathway regulates the expression of a common set of targets required for synaptic maturation and cell-type-specific targets enriched for cell-surface proteins regulating wiring specificity. Transcription factors in the cascade regulate the expression of the same wiring genes in complex ways, including activation in one cell type and repression in another. We show that disruption of the ecdysone pathway generates specific defects in dendritic and axonal processes and synaptic connectivity, with the order of transcription factor expression correlating with sequential steps in wiring. We also identify shared targets of a cell-type-specific transcription factor and the ecdysone pathway that regulate specificity. We propose that neurons integrate a global temporal transcriptional module with cell-type-specific transcription factors to generate different cell-type-specific patterns of cell recognition molecules regulating wiring.

Circadian rhythms mediate malaria transmission potential.

Malaria transmission begins when infected female Anopheles mosquitos deposit Plasmodium parasites into the mammalian host's skin during a bloodmeal. The salivary gland-resident sporozoite parasites migrate to the bloodstream, subsequently invading and replicating within hepatocytes. As Anopheles mosquitos are more active at night, with a 24-hour rhythm, we investigated whether their salivary glands are under circadian control, anticipating bloodmeals and modulating sporozoite biology for host encounters. Here we show that approximately half of the mosquito salivary gland transcriptome, particularly genes essential for efficient bloodmeals such as anti-blood clotting factors, exhibits circadian rhythmic expression. Furthermore, we demonstrate that mosquitoes prefer to feed during nighttime, with the amount of blood ingested varying cyclically throughout the day. Notably, we show a substantial subset of the sporozoite transcriptome cycling throughout the day. These include genes involved in parasite motility, potentially modulating the ability to initiate infection at different times of day. Thus, although sporozoites are typically considered quiescent, our results demonstrate their transcriptional activity, revealing robust daily rhythms of gene expression. Our findings suggest a circadian evolutionary relationship between the vector, parasite and mammalian host that together modulate malaria transmission.

Zooming into the Lab: Perspectives on Maintaining Undergraduate Biological Research through Computationally Adapted Remote Learning in Times of Crisis.

At the onset of the COVID-19 pandemic, many academic institutions attempted to limit viral spread throughout their communities by suspending face-to-face student instruction. The rapid transition from in-person to remote learning dramatically altered student-instructor interactions and ushered in a new set of educational challenges. Despite recent publications by experienced researchers that address the impacts of remote instruction on undergraduate research at a holistic level, we currently lack evidence for successful implementation of best practices in a remote research environment during the COVID-19 pandemic. Therefore, to enhance remote scientific experiences and improve the skills of young biologists facing uncertain challenges in their future academic careers, we make nine recommendations for best practices in maintaining quality undergraduate research experiences, especially for computationally adapted projects, during online learning periods in times of crisis. Based on our experience participating in an undergraduate Stanford Summer Research Program that was conducted entirely remotely during the summer of 2020, we describe nine recommendations for best practices that institutions, faculty mentors, and undergraduate mentees can execute to maintain a high quality of biological research. Further elucidating the ways in which distance learning can be improved at the undergraduate research level will offer insights into making the most out of remote biological research in the months and years ahead.