Biology subjects

Caldwell, J.

Publications and source records attributed to Caldwell, J..

5 recordsLinked to original sources

bioRxiv2026

Unlocking Targeted Underwater Delivery of Coral Probiotics

The rapid global decline of coral reefs has intensified the need for innovative conservation strategies, including microbial therapies to enhance coral health and resilience. A major limitation, however, is the lack of effective delivery systems for administering Beneficial Microorganisms for Corals (BMCs). In this study, we present natural, biodegradable systems for the underwater delivery of probiotic bacteria to corals. Three customized alginate-based delivery formats (beads, hydrogels, and filaments) were developed and loaded with the probiotic Pseudoalteromonas peptidolytica. The materials were loaded with the bacterium at an average concentration of 10^(4) CFU/g of dry polymer and engineered to sink underwater while keeping their structural integrity over time. In vitro assays showed controlled release kinetics, with encapsulated probiotics remaining viable and capable of replication. In vivo experiments compared syringe-based inoculation with the application of alginate beads, hydrogels, and filaments to corals. Microbiome analyses performed before and after inoculation confirmed successful probiotic colonization following deployment of the alginate-based delivery systems. Relative abundance of the probiotic genus Pseudoalteromonas increased markedly in treated corals, reaching 11.5 % after 48 h with alginate beads, 12.7 % after 48 h with hydrogels, and 12.6 % after 24 h with filaments. Furthermore, the degradation mechanisms of the three delivery systems were investigated. As the first biomaterial-based underwater delivery systems specifically engineered for coral probiotics, these alginate-based materials provide a promising foundation for advancing microbial therapies in both controlled aquaria and natural reef environments.

bioengineering↗

bioRxiv2026

Adeno-associated virus serotype tropism and transduction in murine dorsal root ganglia following direct injection.

The peripheral nervous system (PNS) is highly heterogeneous, comprised of diverse subclasses of motor and sensory neurons. Optogenetics offers a high-resolution approach for interrogating neural circuits; however, optogenetic proteins must be selectively delivered to defined neuronal circuits in order to elucidate circuit-specific functional mechanisms. Adeno-associated viral vectors (AAVs) are widely used to deliver transgenes to the nervous system due to their relative safety and strong transgene expression. Multiple AAV serotypes are in common use, each capable of preferentially transducing distinct tissues and neuronal populations. However, characterization of the transduction behavior of these serotypes in the PNS, particularly in the dorsal root ganglia (DRG) and sensory nervous system (SNS), remain limited. This study evaluated the transduction efficiency of AAV8, AAV9, AAV2re, and PHP.S following direct intraganglionic injection into the DRG. AAV8, AAV9, and PHP.S exhibited comparable transduction efficiencies, whereas AAV2re transduced more than twofold fewer neurons. Despite similar overall efficiencies between AAV8, AAV9, and PHP.S, the neuronal volume distributions of transduced neurons were serotype-dependent. These results demonstrate that AAV serotype selection influences both the extent and size of transduced DRG neurons, indicating that serotype selection should be considered carefully when designing experiments that target peripheral sensory circuits.

neuroscience↗

bioRxiv2026

Multi-site temporal control of optogenetic stimulation enhances firing frequencies in peripheral nerves

We find that multi-site temporal control of optogenetic photostimulation in peripheral nerves can enhance firing rates by overcoming the intrinsic limitation of opsin photophysics. The benefits of multi-site optogenetic stimulation were demonstrated with three approaches: (1) in silico modeling, (2) ex vivo in the sciatic nerve, and (3) in vivo in the vagus nerve. An in silico model of multi-site optogenetic stimulation was developed in two Hodgkin and Huxley type neuron models, that supported our hypothesis. The ex vivo sciatic nerve showed an increase in firing frequency that is physiologically relevant for functional control. The technique was then applied in vivo for optogenetic vagus nerve stimulation resulting in significant changes in heart rate compared with standard methods of single-site stimulation. Improving the control of optogenetically induced neural firing will have broad impacts for future developments in optical nerve interfaces and brain-machine interfaces.

neuroscience↗

bioRxiv2025

Discovery of first-in-class inhibitors of the TRF1-TIN2 protein-protein interaction by fragment screening

TRF1 is a subunit of the shelterin complex that binds to and protects the linear ends of chromosomes known as telomeres. Both genetic deletion and chemical inhibition of TRF1 have been shown to block the growth of lung carcinoma, glioblastoma, and renal cell carcinoma in mice without affecting mouse survival or tissue function, making TRF1 a potential therapeutic target in cancer1-3. Here, we report the discovery of a series of fragment hits that bind at the interface between the TRFH domain of TRF1 (TRF1TRFH) and a peptide of TIN2 (TIN2TBM), an interaction essential for the recruitment of TRF1 to shelterin, using X-ray crystallography (XChem) and ligand-observed NMR (LO-NMR) fragment screening. We discovered a first-in-class inhibitor of the TRF1-TIN2 interaction (compound 40) that binds to TRF1TRFH with a KD of 29 M (95% CI: 20 - 41 M), displaces a TIN2 probe with an IC50 of 67 {+/-} 28 M, and expels TRF1 from purified shelterin. Aided by a novel crystal system of TRF1TRFH, we characterised fragments binding in a hotspot at the TRF1-TIN2 interface which will serve as a starting point for the structure-guided development of potent inhibitors of TRF1 protein-protein interactions to disrupt shelterin complex assembly.

biochemistry↗

bioRxiv2019

Case-control design identifies ecological drivers of endemic coral diseases

Endemic disease transmission is an important ecological process that is challenging to study because of low occurrence rates. Here, we investigate the ecological drivers of two coral diseases -- growth anomalies and tissue loss -- affecting five coral species. We first show that a statistical framework called the case-control study design, commonly used in epidemiology but rarely applied to ecology, provided high predictive accuracy (67-82%) and disease detection rates (60-83%) compared with a traditional statistical approach that yielded high accuracy (98-100%) but low disease detection rates (0-17%). Using this framework, we found evidence that 1) larger corals have higher disease risk; 2) shallow reefs with low herbivorous fish abundance, limited water motion, and located adjacent to watersheds with high fertilizer and pesticide runoff promote low levels of growth anomalies, a chronic coral disease; and 3) wave exposure, stream exposure, depth, and low thermal stress are associated with tissue loss disease risk during interepidemic periods. Variation in risk factors across host-disease pairs suggests that either different pathogens cause the same gross lesions in different species or that the same disease may arise in different species under different ecological conditions.

ecology↗