Biology subjects

Kerwin, P.

Publications and source records attributed to Kerwin, P..

3 recordsLinked to original sources

bioRxiv2026

Abdominal-B regulates the male seminal fluid transferome and new female fecundity factors required for sperm sex peptide binding

Seminal fluid proteins determine reproductive success in a wide range of animals. In the Drosophila male accessory gland, seminal fluid is mainly produced by two cell types, a vast majority of main cells and a small number of secondary cells that possess a specialized secretory apparatus with unusually enlarged dense core granule vesicles. Loss of Abdominal-B expression from secondary cells in the enhancer mutant iab-6cocu disrupts their transcriptional and secretory identity. Consequently, mutant males fail to induce the long-term post-mating response in females, which is characterized by a loss of receptivity and sustained egg laying. Here, we determine how secondary cells shape the seminal transferome and the female response by assessing iab-6cocu male accessory gland and female mate reproductive tract proteomes. We find downregulation of seminal fluid proteins that constitute a signaling network that enables sperm binding and the sustained action of the key regulator Sex peptide and identify two new Sex peptide network proteins crucial for female fecundity, Cornutus (CG1701) and Hanrej (CG42564). Cornutus is required for mating dependent dense core granule vesicle release, providing a link between the products of these compartments and the female long-term post-mating response. Our data highlights the importance of secondary cell signaling and secretion for overall seminal fluid composition and Sex peptide network function as well as the interdependence of main and secondary cells and their secretory products, advancing the general understanding of how seminal fluid signaling pathways modulate female physiology, sperm use and offspring production.

physiology↗

bioRxiv2023

Network-based elucidation of colon cancer drug resistance by phosphoproteomic time-series analysis

Aberrant signaling pathway activity is a hallmark of tumorigenesis and progression, which has guided targeted inhibitor design for over 30 years. Yet, adaptive resistance mechanisms, induced by rapid, context-specific signaling network rewiring, continue to challenge therapeutic efficacy. By leveraging progress in proteomic technologies and network-based methodologies, over the past decade, we developed VESPA--an algorithm designed to elucidate mechanisms of cell response and adaptation to drug perturbations--and used it to analyze 7-point phosphoproteomic time series from colorectal cancer cells treated with clinically-relevant inhibitors and control media. Interrogation of tumor-specific enzyme/substrate interactions accurately inferred kinase and phosphatase activity, based on their inferred substrate phosphorylation state, effectively accounting for signal cross-talk and sparse phosphoproteome coverage. The analysis elucidated time-dependent signaling pathway response to each drug perturbation and, more importantly, cell adaptive response and rewiring that was experimentally confirmed by CRISPRko assays, suggesting broad applicability to cancer and other diseases.

systems biology↗

bioRxiv2023

Distinct representations of innate and learned threats within the thalamic-amygdala pathway

Behavioral flexibility and timely reactions to salient stimuli are essential for survival. The subcortical thalamic-basolateral amygdala (BLA) pathway serves as a shortcut for salient stimuli ensuring rapid processing. Here, we show that BLA neuronal and thalamic axonal activity mirror the defensive behavior evoked by an innate visual threat as well as an auditory learned threat. Importantly, perturbing this pathway compromises defensive responses to both forms of threats, in that animals fail to switch from exploratory to defensive behavior. Despite the shared pathway between the two forms of threat processing, we observed noticeable differences. Blocking beta-adrenergic receptors impair the defensive response to the innate but not the learned threats. This reduced defensive response, surprisingly, is reflected in the suppression of the activity exclusively in the BLA, as the thalamic input response remains intact. Our side-by-side examination highlights the similarities and differences between innate and learned threat-processing, thus providing new fundamental insights.

neuroscience↗