Biology subjects

Ravichandran, V.

Publications and source records attributed to Ravichandran, V..

4 recordsLinked to original sources

bioRxiv2026

Serpin-Driven Green Camouflage and NIR Fluorescence in Frogs

Animals have evolved multiple strategies to generate optical traits and coloration. While most amphibians rely on a three-dimensional arrangement of chromatophores in the skin, hundreds of arboreal frog species achieve leaf-like green color through a different mechanism involving reduced pigmentation, subcutaneous biological mirrors, and high concentrations of the blood-derived pigment biliverdin. Although biliverdin is rapidly excreted in most vertebrates, hylid and centrolenid frogs can retain it through the binding to a serpin-family protein (BBS). Here we show that BBSs bind biliverdin with high affinity (Kd < 10 nM), comparable to hormone-receptor interactions. This interaction alters biliverdins spectral signature in ways that resemble those of green-leaf pigments. BBSs from different species exhibit distinct biophysical properties, accounting for interspecific differences in color saturation and hue. Unlike most serpins in vivo, BBS of the glassfrog Teratohyla pulverata is naturally cleaved, yielding a highly thermostable, thermodynamically favored protein, without loss of affinity. Using custom-designed hyperspectral photoacoustic tomography (PAT), we demonstrate that BBS is widely distributed throughout the body, contributing to whole-body color and camouflage. Furthermore, we show that BBSs emit near-infrared (NIR) fluorescence (>700 nm) rendering these frogs fluorescent in a spectral region where biological tissues are largely transparent. Together, BBSs shed light on serpin evolution, protein thermostability, amphibian color diversity, and the development of NIR molecular probes.

biochemistry↗

bioRxiv2024

Resource Quality Differentially Impacts Daphnia Interactions with Two Parasites

Resource quality can have conflicting effects on host-parasite interactions; for example, higher resource quality might increase host investment in immune function, or conversely, might permit greater parasite reproduction. Thus, anticipating the impact of changing resource quality on host- parasite interactions is challenging, especially because we often lack a mechanistic understanding of how resource quality influences host physiology and fitness to alter infection outcomes. We investigated whether there are generalizations in how resource quality affects multiple host clones interactions with different parasites. We used the Daphnia freshwater zooplankton model system to experimentally investigate how a resource quality gradient from high-quality green algae to poor-quality cyanobacteria diets influences host fitness, physiology, and infection by two parasites: a bacterium, Pasteuria ramosa, and a fungus, Metschnikowia bicuspidata. We ran a separate experiment for each parasite using a factorial design with four diets, two Daphnia dentifera host clones, and parasite-inoculated and uninoculated treatments (16 treatments per experiment). Diet strongly influenced infection by the fungus but not the bacterium. These relationships between diet and infection cannot be explained by changes in feeding rate (and, therefore, parasite exposure). Instead, the impact of diet on fungal infection was associated with impacts of diet on the earliest stage of infection: hosts that fed on poor quality diets had very few attacking spores in their guts. Diet did not significantly influence host immune responses. Diet influenced spore production differently for the two parasites, with reduced resource quality limiting the number of fungal spores and the size (but not number) of bacterial spores. Diet, host clone, and infection all affected host fitness. Interestingly, diet influenced the impact of the bacterium, a parasitic castrator that induces gigantism; for one clone, infected hosts fed high quality diets still produced a substantial number of offspring, whereas resource limitation hindered gigantism. Finally, there were often costs of resisting infection, though these generally were not affected by diet. Overall, we show that resource quality differentially impacts the exposure, infection, and proliferation processes for different parasites and host clones, which highlights the need to use multi-genotype and multi-parasite studies to better understand these complex interactions.

ecology↗

bioRxiv2024

KAT5 Acetylates Human Chromatin Protein PC4 to promote DNA Repair

Human positive coactivator 4 (PC4), is a highly abundant non-histone chromatin protein involved in diverse cellular processes, including transcription regulation, genome organization, DNA repair, etc. The majority of PC4 exists in a phosphorylated state in cells, which impinges its acetylation by p300 and thereby inhibits its double-stranded DNA binding ability and transcriptional co-activator function. Recently, we have shown that PC4 interacts with linker histone H1 in its phosphorylated state, and this interaction is important for PC4- mediated chromatin compaction. PC4 was also found to be an activator of non-homologous end joining and DSB repair activity. Knockdown of PC4 causes drastic decompaction and enhanced autophagy in the cells. Mechanistically, in the absence of PC4, the genome becomes highly vulnerable to DNA damage with an altered epigenetic landscape. Here, we report that other than p300, PC4 also gets acetylated by DNA repair facilitating lysine acetyltransferase KAT5 (Tip60), at K80 residue when the cells are subjected to DNA damage. The vulnerability of DNA in PC4 devoid cells could be substantially reduced by reintroducing wild-type PC4 to the cells but not the mutant PC4 (K80R PC4), defective in KAT5-mediated acetylation. Presumably, KAT5-mediated acetylation of PC4 at K80 residue facilitates the DNA repair machinery at the damage site and thus contributes to DNA damage repair, a process that could be of high significance both in cancer and in aging.

molecular biology↗

bioRxiv2018

Towards automation of germline variant curation inclinical cancer genetics

Cancer care professionals are confronted with interpreting results from multiplexed gene sequencing of patients at hereditary risk for cancer. Assessments for variant classification now require orthogonal data searches, requiring aggregation of multiple lines of evidence from diverse resources. The burden of evidence for each variant to meet thresholds for pathogenicity or actionability now poses a growing challenge for those seeking to counsel patients and families following germline genetic testing. A computational algorithm that automates, provides uniformity and significantly accelerates this interpretive process is needed. The tool described here, Pathogenicity of Mutation Analyzer (PathoMAN) automates germline genomic variant curation from clinical sequencing based on ACMG guidelines. PathoMAN aggregates multiple tracks of genomic, protein and disease specific information from public sources. We compared expert manually curated variant data from studies on (i) prostate cancer (ii) breast cancer and (iii) ClinVar to assess performance. PathoMAN achieves high concordance (83.1% pathogenic, 75.5% benign) and negligible discordance (0.04% pathogenic, 0.9% benign) when contrasted against expert curation. Some loss of resolution (8.6% pathogenic, 23.64% benign) and gain of resolution (6.6% pathogenic, 1.6% benign) was also observed. We highlight the advantages and weaknesses related to the programmable automation of variant classification. We also propose a new nosology for the five ACMG classes to facilitate more accurate reporting to ClinVar. The proposed refinements will enhance utility of ClinVar to allow further automation in cancer genetics. PathoMAN will reduce the manual workload of domain level experts. It provides a substantial advance in rapid classification of genetic variants by generating robust models using a knowledge-base of diverse genetic data https://pathoman.mskcc.org.

genetics↗