Biology subjects

McCauley, M.

Publications and source records attributed to McCauley, M..

5 recordsLinked to original sources

bioRxiv2026

Thermal pre-treatment of algal symbiont species differentially affects coral development

The foundation of coral reef ecosystems centered around the nutritional relationship between corals and intracellular algal symbionts. Although these symbioses are highly obligate for coral hosts, many partnerships are re-established anew with each coral generation. Furthermore, climate change destabilizes the symbiosis, and the cellular mechanisms underlying successful symbiont colonization of hosts and host development, and how they are affected by thermal stress are poorly understood. Here, we explored the effect of algal species and thermal treatments on symbiont and host cell proliferation by offering Acropora tenuis larvae one of four algal species pre-exposed to elevated or ambient temperature. In addition, we characterized the cell-surface glycome of each species-temperature combination to understand its role in symbiont recognition and proliferation. We found that thermal pre-treatment negatively affected algal photosynthetic efficiency and initial symbiont density in hosts, but did not affect symbiont colonization rate or cell proliferation. In contrast, host cell proliferation was affected in a species-specific manner. Thermal pre-treatment of B. minutum and D. trenchii negatively affected host cell proliferation compared to control symbionts, whereas thermal treatment of S. microadriaticum did not affect developmental outcomes. Further, uptake of thermally pre-treated D. trenchii decreased host cell proliferation below that of larvae not offered any symbionts, indicating that this relationship is costly to host development despite the high thermal tolerance of this species. Algal surface glycan composition varied across species but not by thermal pre-treatment, suggesting reductions in density of thermally pre-treated algae may be due to changes in physiology rather than altered surface chemistry. Further, variation in glycan abundance across species did not track differences in colonization rate or symbiont density, hinting towards a smaller role of glycans in host-symbiont specificity.

cell biology↗

bioRxiv2025

Advancing (-)-Premarineosin A as a Potent Antimalarial Therapeutic via Metabolic Engineering and Late-Stage Derivatization

Diversification of structurally complex natural products remains a key challenge in the discovery of next-generation therapeutics. Premarineosin A, a potent and selective antimalarial natural product, is a promising yet underexplored scaffold due to limited availability and synthetic complexity. In this work, we overcome both barriers by coupling metabolic engineering with late-stage derivatization, enabling the first systematic exploration of the premarineosin A scaffold. Rational engineering of Streptomyces eitanensis, encoding a (-)-premarineosin A biosynthetic gene cluster, increased titers over 200-fold. Sustainable production of (-)-premarineosin A enabled a unique semi-synthetic and biocatalytic derivatization campaign. In this first structure-activity relationship study of premarineosin A, we accessed a suite of novel analogs, including a C12-brominated derivative with nanomolar potency (EC50 < 5 nM). This work establishes (-)-premarineosin A as a tractable and evolvable antimalarial scaffold, demonstrating how chemical biology approaches can unlock new structural and pharmacological space from complex microbial metabolites.

microbiology↗

bioRxiv2024

Genomic sequencing and neutralizing serological profiles during acute dengue infection: A 2017 cohort study in Nepal

Dengue virus (DENV) is a mosquito-borne flavivirus that poses a threat to nearly 50% of the global population. DENV has been endemic in Nepal since 2006; however, little is known about how DENV is evolving or the prevalence of anti-DENV immunity within the Nepalese population. To begin to address these gaps, we performed a serologic and genetic study of 49 patients from across Nepal who presented at central hospitals during the 2017 dengue season with suspected DENV infection. Of the 49 subjects assessed, 21 (43%) were positive for DENV NS1 antigen; of these; 5 were also anti-DENV IgM+ IgG+; 7 were DENV IgM+ IgG-, 2 were IgM- IgG+, and 7 were IgM- IgG- by specific ELISAs. Seven of the 21 NS1+ sera were RNA+ by RT-PCR (six DENV2, one DENV3), suggesting that DENV2 was the dominant serotype in our cohort. Whole-genome sequencing of two DENV2 isolates showed similarity with strains circulating in Singapore in 2016, and the envelope genes were also similar to strains circulating in India in 2017. DENV-neutralizing antibodies (nAbs) were present in 31 of 47 sera tested (66%); among these, 20, 24, 26, and 12 sera contained nAbs against DENV1, 2, 3, and 4 serotypes, respectively. Serology analysis suggested that 12 (26%) and 19 (40%) of the 49 subjects were experiencing primary and secondary DENV infections, respectively. Collectively, our results provide evidence for current and/or past exposure to multiple DENV serotypes in our cohort, and the RNA analyses further indicate that DENV2 was the likely dominant serotype circulating in Nepal in 2017. These data suggest that expanded local surveillance of circulating DENV genotypes and population immunity will be important to effectively manage and mitigate future dengue outbreaks in Nepal.

genomics↗

bioRxiv2022

Symbiosis-driven development in an early branching metazoan

Microbes can initiate developmental gene regulatory cascades in animals. The molecular mechanisms underlying microbe-induced animal development and the evolutionary steps to integrate microbial signals into regulatory programs remain poorly understood. In the upside-down jellyfish Cassiopea xamachana, a dinoflagellate endosymbiont initiates the life stage transition from the sessile polyp to the sexual medusa. We found that metabolic products derived from symbiont carotenoids may be important to initiate C. xamachana development, in addition to expression of conserved genes involved in medusa development of non-symbiotic jellyfish. We also revealed the transcription factor COUP is expressed during metamorphosis, potentially as a co-regulator of nuclear receptor RXR. These data suggest relatively few steps may be necessary to integrate symbiont signals into gene regulatory networks and cements the role of the symbiont as a key trigger for life history transition in C. xamachana.

developmental biology↗

bioRxiv2020

Protein hyperacylation links mitochondrial dysfunction with nuclear organization

Cellular metabolism is linked to epigenetics, but the biophysical effects of metabolism on chromatin structure and implications for gene regulation remain largely unknown. Here, using a broken tricarboxylic acid (TCA) cycle and disrupted electron transport chain (ETC) exemplified by succinate dehydrogenase subunit C (SDHC) deficiency, we investigated the effects of metabolism on chromatin architecture over multiple distance scales [nucleosomes ([~]102 bp), topologically-associated domains (TADs; [~]105 - 106 bp), and chromatin compartments (106 - 108 bp)]. Metabolically-driven hyperacylation of histones led to weakened nucleosome positioning in multiple types of chromatin, and we further demonstrate that lysine acylation directly destabilizes histone octamer-DNA interactions. Hyperacylation of cohesin subunits correlated with decreased mobility on interphase chromatin and increased TAD boundary strength, suggesting that cohesin is metabolically regulated. Erosion of chromatin compartment distinctions reveals metabolic regulation of chromatin liquid-liquid phase separation. The TCA cycle and ETC thus modulate chromatin structure over multiple distance scales.

cell biology↗