Biology subjects

Trinca, T. M.

Publications and source records attributed to Trinca, T. M..

3 recordsLinked to original sources

bioRxiv2026

Drosben, an affordable system for scalable survival analysis in Drosophila

Survival analysis is a workhorse assay in Drosophila research to evaluate somatic fitness. It is indispensable in the study of ageing and insightful in immunity, metabolism, radiobiology, toxicology, ecology, and others. While conceptually simple, lifespan measurement is labour-intensive because it requires the continuous manual maintenance of large experimental cohorts. Here, we describe Drosben, an approach that combines a 3D-printed device to transfer flies from several vials simultaneously, a paper system for quick data recording and accompanying software that automatically digitalises life tables for analysis. We show that using Drosben reduces the time investment to perform lifespan assays by [~]85%, with improved speed regardless of experience handling Drosophila vials. Using Drosben, we address the effects on longevity of chronic feeding of indole-acetic acid (IAA), naphthalene-acetic acid (NAA) and trimethoprim (TMP) - compounds used to control heterologous targeted protein degradation systems. We find that IAA and NAA have noticeable deleterious effects while TMP has a small protective effect specifically in females. We further show that strong static magnetic fields do not affect Drosophila lifespan. Our work suggests that Drosben can cheaply accelerate research where lifespan is used as a life history trait.

physiology↗

bioRxiv2026

Orphan GPR84 facilitates uropod de-adhesion to terminate leukocyte diapedesis during inflammation

Leukocyte migration through venular walls is an essential component of effective immunity. While the key molecular players driving the initial steps of this response are known, the terminating signals remain unclear. Here, we have identified a conserved role for GPR84 family GPCRs in successful completion of the final stages of leukocyte extravasation through acutely inflamed vessels. The integration of high resolution intravital imaging with cell-specific genetics revealed that genetic deficiency of GPR84 orthologues in mice and Drosophila, results in defective detachment of transmigrating immune cells from vessel walls. Mechanistically, transcriptomics revealed GPR84-deficient neutrophils exhibit defective actin cytoskeletal regulation and cellular adhesion/de-adhesion. Consistent with this, our fly-murine pipeline shows that GPR84 supports localized and dynamic Rho activation to enable detachment of the immune cell uropod from vessel exit sites. Moreover, pharmacological blockade of GPR84 signaling dampened immune cell migration in multiple murine acute inflammatory settings. Collectively, our findings present GPR84 as a novel physiological regulator of immune cell extravasation that is amenable to therapeutic targeting for modulating leukocyte infiltration into inflamed tissues. SummaryHere we identify the GPR84 family of GPCRs as key regulators of effective immune cell extravasation in vivo. Mechanistically, through integrating genetically tractable Drosophila and murine in vivo models, we show how leukocyte GPR84 supports dynamic Rho-dependent detachment of stretched uropods as these cells exit vessels.

immunology↗

bioRxiv2023

ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways

Human cytomegalovirus (HCMV) is a major human pathogen whose life-long persistence is enabled by its remarkable capacity to systematically subvert host immune defences. In exploring the finding that HCMV infection upregulates tumor necrosis factor receptor 2 (TNFR2), a ligand for the pro-inflammatory anti-viral cytokine TNFa, we discovered the underlying mechanism was due to targeting of the protease, A Disintegrin And Metalloproteinase 17 (ADAM17). ADAM17 is the prototype sheddase, a family of proteases that cleaves other membrane-bound proteins to release biologically active ectodomains into the supernatant. HCMV impaired ADAM17 surface expression through the action of two virally-encoded proteins in its UL/b region, UL148 and UL148D. Proteomic plasma membrane profiling of cells infected with a HCMV double deletion mutant for UL148 and UL148D with restored ADAM17 expression, combined with ADAM17 functional blockade, showed that HCMV stabilized the surface expression of 114 proteins (p<0.05) in an ADAM17-dependent fashion. These included known substrates of ADAM17 with established immunological functions such as TNFR2 and Jagged1, but also numerous novel host and viral targets, such as Nectin1, UL8 and UL144. Regulation of TNF-induced cytokine responses and NK inhibition during HCMV infection were dependent on this impairment of ADAM17. We therefore identify a viral immunoregulatory mechanism in which targeting a single sheddase enables broad regulation of multiple critical surface receptors, revealing a paradigm for viral-encoded immunomodulation. Significance statementHuman cytomegalovirus (HCMV) is an important pathogen, being the commonest infectious cause of brain damage to babies and the primary reason for hospital readmissions in transplant recipients. Even though HCMV induces the strongest immune responses by any human pathogen, it evades host defences and persists for life. This study describes a novel immunoregulatory strategy through which HCMV modulates multiple immune pathways simultaneously, by targeting a single host protein. HCMV UL148 and UL148D impair the maturation of the sheddase, A Disintegrin And Metalloproteinase 17, profoundly altering surface expression of numerous immunoregulatory proteins. This is the first description of viral genes targeting this pathway. Our findings may be relevant for future viral therapies and understanding the impact of HCMV in developmental biology.

microbiology↗