Biology subjects

O'Reilly, A. M.

Publications and source records attributed to O'Reilly, A. M..

4 recordsLinked to original sources

bioRxiv2026

Starve-Feed Cycles Direct Quiescence to Proliferation Transitions in Drosophila Follicle Stem Cells via Transcriptional Regulation

Stem cell quiescence is a reversible state in which cells temporarily exit the cell cycle but remain poised to reenter, on cue. Robust protection of the balance between stem cell quiescence and proliferation (Q->P) is critical for long-term tissue health. Proliferation without proper resources drives disease states including cancer or birth defects. Conversely, extended periods of quiescence can lead to irreversible senescence, causing stem cell loss, aging symptoms, and vulnerability to oncogenic transformation. Diet is a central regulator of Q->P. Tissue stem cells are particularly impacted, entering periods of quiescence during nutrient restriction, with rapid induction of proliferation upon feeding. We demonstrated previously that the Hedgehog (Hh) signaling pathway is necessary and sufficient for controlling Q->P responses to dietary changes in epithelial Follicle Stem Cells (FSCs) in the fly ovary. The Hh effector, Cubitus Interruptus (Ci), is a transcriptional regulator that mediates the feeding response. To identify Ci-induced Q->P regulators, we labeled transcripts that are induced in FSCs during the 6-hour Q->P timecourse using thiouracil tagging (TU-tagging), and sequenced TU-tagged messages versus Input to prioritize candidates. Unexpectedly, cell cycle regulators were not induced, suggesting that other mechanisms control Q->P in FSCs. We describe a sequential screening approach that uncovered seven novel, feeding-dependent Q->P regulators, including a cholesterol transporter and, surprisingly, glial and neuronal regulators. Our results highlight the importance of dynamic regulation of gene expression for translation of dietary signals by stem cells, uncovering new pathways for mechanistic investigation.

genetics↗

bioRxiv2021

Flying in the Face of Adversity: A Drosophila-based Virtual CURE Provides Semester-long Authentic Research Opportunity to the Flipped Classroom.

A call for the integration of research experiences into all biology curricula has been a major goal for educational reform efforts nationally. Course-Based Undergraduate Research Experiences (CUREs) have been the predominant method of accomplishing this, but their associated costs and complex design can limit their wide adoption. In 2020, the COVID-19 pandemic forced programs to identify unique ways to still provide authentic research experiences while students were virtual. We report here a full guide for the successful implementation of a semester-long virtual CURE that uses Drosophila behavioral assays to explore the connection between pain and addiction with the use of a "lab-in-a-box" sent home to students. Individual components were piloted across three semesters and launched as a 100-level introductory course with 19 students. We found that this course increased science identity and successfully improved key research competencies as per the Undergraduate Research Student Self-Assessment (URSSA) survey. This course is ideal for flipped classrooms ranging from introductory biology to upper-level neuroscience courses and can be integrated directly into the lecture period without the need for building a new course. Given the low cost, recent comfort with virtual learning environments, and the current proliferation of flipped biology classrooms following the 2020 pandemic, this curriculum could serve as an ideal project-based active-learning tool for equitably increasing access to authentic research experiences.

scientific communication and education↗

bioRxiv2020

Interactions between axon-like projections extended by Drosophila Follicle Stem Cells dictate cell fate decisions

Stem cells cycle between periods of quiescence and proliferation to promote healthy tissue aging. Once proliferation is initiated, mechanisms that control the balance between self-renewal and differentiation must be engaged to ensure maintenance of stem cell pools until the next quiescent cycle occurs. Here, we demonstrate that dynamic axon-like projections extended by Follicle Stem Cells (FSCs) in the Drosophila ovary control the self-renewal-differentiation balance. Known axon growth regulators still life and sickie are necessary and sufficient for FSC projection growth, mediating organization of germline cyst architecture during follicle formation, controlling targeting of projections to FSCs or germ cells, and regulating expression of the cell fate determinants Eyes Absent (Eya) and Castor (Cas). Our results support a model in which FSC projections function similarly to axons, providing structural organization to a dynamic organ while mediating communication between distinct cell types to effect the key cell fate decision to self-renew or differentiate.

developmental biology↗

bioRxiv2019

Cholesterol deprivation induces TGFβ signaling to promote basal differentiation in pancreatic cancer

Oncogenic transformation alters the metabolism of cellular nutrients to sustain tumor growth. We here define a mechanism by which modifications in cholesterol metabolism control the formation of pancreatic ductal adenocarcinoma (PDAC). Disruption of distal cholesterol biosynthesis by means of conditional inactivation of Nsdhl in mice bearing a tumor-inducing Kras mutation (KrasG12D) prevented PDAC formation in the context of a heterozygous Trp53f/+genotype without impairing normal pancreatic development. In mice with pancreatic Nsdhl ablation and homozygous loss of Trp53, the emerging tumors presented with the aggressive basal (mesenchymal) phenotype as opposed to the classic (glandular) PDAC. This paralleled significantly reduced expression of cholesterol metabolic pathway genes in human basal PDAC subtype. Mechanistically, we demonstrate that genetic or metabolic cholesterol deprivation stabilizes the transforming growth factor beta (TGF{beta}) receptor to activate pro-mesenchymal effectors in human and murine PDAC, providing a direct mechanism by which cholesterol metabolism can condition tumor differentiation.

cancer biology↗