Biology subjects

Forster, D.

Publications and source records attributed to Forster, D..

4 recordsLinked to original sources

bioRxiv2025

Regional Vulnerability of Cardiac Chambers to Radiotherapy: A Multi-Omics Perspective

The heart is highly vulnerable to radiotherapy (RT)-induced injury, leading to molecular and structural remodeling collectively termed radiation-induced cardiac toxicity (RICT). Although several biological pathways have been implicated, the regional, cardiac-specific molecular responses to radiation exposure remain incompletely understood. Here, a multi-omics approach was adopted to longitudinally characterise the unique responses to radiation of the heart base (including ventricular base and right atrium), or the heart apex. Ventricular base irradiation induced a cardiomyopathy phenotype, with pronounced molecular perturbations in metabolism and electrical conduction, while changes related to tissue structure were predominant following apex-directed RT. In the right atrium, irradiation drives fibrotic tissue remodelling, leading to an increased propensity for atrial fibrillation, underpinned by changes in sarcomere organisation. This study represents a comprehensive characterisation of differential spatiotemporal radiation effects in the heart and highlights biological and functional pathways that are potentially clinically actionable for cardiac radioprotection and monitoring.

cell biology↗

bioRxiv2024

CCR2-driven monocyte recruitment is protective against radiotherapy-induced intestinal toxicity

Radiotherapy (RT) is essential in treating abdominal and pelvic cancers but often damages the healthy tissues, particularly the intestines, leading to radiation-induced toxicities with limited treatment options. While the immune system is known to help regulate tissue damage, immune mechanisms involved in RT-induced intestinal toxicity are not fully understood. Following CT-guided localised intestinal irradiation, single-cell RNA sequencing (scRNA-seq) and flow cytometry revealed RT-induced chemokine-dependent recruitment of innate immune cells. Deletion of C-C chemokine receptor (Ccr)1, Ccr2, Ccr3 and Ccr5, blocked recruitment and worsened radiation induced toxicities, suggesting an important role for an innate immune cell population in limiting RT-mediated bowel damage. Furthermore, CCR2-deficient mice showed exacerbated weight loss and intestinal permeability, while the transfer of Ly6C+ monocytes alleviated symptoms. Mechanistically, IL-17 cytokine production by group 3 innate lymphoid cells (ILC3s), a critical factor in maintaining intestinal barrier integrity, was found to be reduced in irradiated CCR2-/-, however the transfer of Ly6C+ monocytes resulted in increased IL-17 levels. These findings demonstrate the critical importance of CCR2-mediated monocyte recruitment in mitigating RT-induced toxicities. One Sentence SummaryCCR2-mediated monocyte recruitment protects against RT-induced intestinal toxicity via IL-17, highlighting a therapeutic target.

immunology↗

bioRxiv2022

Acute manipulation and real-time visualization of membrane trafficking and exocytosis in Drosophila

Intracellular trafficking of secretory proteins plays key roles in animal development and physiology, but tools for investigating dynamics of membrane trafficking have been limited to cultured cells. Here we present a system that enables acute manipulation and real-time visualization of membrane trafficking through reversible retention of proteins in the endoplasmic reticulum (ER) in living multicellular organisms. By adapting the "retention using selective hooks" (RUSH) approach to Drosophila, we show that trafficking of GPI-linked, secreted, and transmembrane proteins can be controlled with high temporal precision in intact animals and cultured organs. We demonstrate the potential of this approach by analyzing the kinetics of ER exit and apical secretion and the spatiotemporal dynamics of tricellular junction assembly in epithelia of living embryos. Furthermore, we show that controllable ER-retention enables tissue-specific depletion of secretory protein function. The system is broadly applicable to visualize and manipulate membrane trafficking in diverse cell types in vivo.

cell biology↗

bioRxiv2020

Evaluating geographic variation within molecular operational taxonomic units (OTUs) using network analyses in Scandinavian lakes

Operational taxonomic units (OTUs) are usually treated as if they are internally uniform in environmental metabarcoding studies of microbial and macrobial eukaryotes, even when the OTUs are being used to infer biogeographic patterns. The OTUs constructed by the program Swarm have underlying network topologies in which nodes represent amplicons and edges represent 1 nucleotide differences between nodes. Such networks can be exploited to search for biogeographic patterns within each OTU. To do this, here we used an available protistan metabarcoding dataset consisting of the hypervariable V4 region of the 18S rRNA locus amplified from 77 lakes collected across Norway and Sweden. The 82 most abundant and wide-spread OTUs constructed by Swarm were evaluated using shortest path, assortativity, and geographical analyses. We found that while pairs of amplicons from the same lake were usually connected directly to each other within the OTUs, these pairs of amplicons from the same lake did not form assortative clusters within the OTUs, and amplicons were not more connected with other amplicons occurring in neighboring lakes than expected by chance. This new approach to looking at within-OTU is applicable to other metabarcoding datasets and we provide code to perform these analyses.

microbiology↗