Biology subjects

Bhattacharya, C.

Publications and source records attributed to Bhattacharya, C..

6 recordsLinked to original sources

bioRxiv2024

Reengineering mRNA lipid nanoparticles for systemic delivery to pancreas

Lipid nanoparticles (LNPs) hold transformative potential for nucleic acid delivery, with applications ranging from clinical use, particularly in COVID-19 vaccines, to gene therapy and cancer immunotherapy. Traditional LNPs are composed of four components: ionizable lipids, cholesterol, helper lipids, and PEGylated lipids. However, a significant hurdle remains the need for more efficient and selective systemic delivery vehicles, as most targets are challenging to reach and primarily accumulate in the liver following intravenous administration, largely due to Apolipoprotein E (ApoE) mediated uptake in the blood. Recent studies have shown that introducing cationic or anionic lipids as a fifth component in the LNPs has resulted in lung- and spleen-specific mRNA expression. In this study, we report that incorporating endogenous ligands, such as vitamins, as a fifth component can enhance the extrahepatic localization of LNPs. Vitamins are highly biocompatible, possess excellent targeting potential, influence immune response, improve cellular uptake, and increase the stability of mRNA LNPs. We developed a library of 100 LNPs containing luciferase mRNA by partially replacing ionizable lipids with this fifth component and evaluated their efficacy both in vitro and in vivo. From comprehensive batch analysis screening, we identified two formulations with cholecalciferol (vitamin D3) as a fifth component that demonstrated selective systemic delivery to the pancreas (> 99%) with high efficacy. Among these, C-CholF3 emerged as the top formulation, exhibiting robust and sustained protein expression in the pancreas for up to 3 days in a dose-dependent manner with minimal toxicity that makes it suitable for repeated administration. Furthermore, C-CholF3 also demonstrated pancreas-specific gene editing in the Ai14 transgenic mouse model, showing high expression of TdTomato. This underscores its translational potential for protein replacement and CRISPR/Cas9-mediated gene editing in currently incurable pancreatic diseases.

bioengineering↗

bioRxiv2022

Supervised Machine Learning Enables Geospatial Microbial Provenance

The recent increase in publicly available metagenomic datasets with geospatial metadata has made it possible to determine location-specific, microbial fingerprints from around the world. Such fingerprints can be useful for comparing microbial niches for environmental research, as well as for applications within forensic science and public health. To determine the regional specificity for environmental metagenomes, we examined 4305 shotgun-sequenced samples from the MetaSUB Consortium dataset - the most extensive public collection of urban microbiomes, spanning 60 different cities, 30 countries, and 6 continents. We were able to identify city-specific microbial fingerprints using supervised machine learning (SML) on the taxonomic classifications, and we also compared the performance of ten SML classifiers. We then further evaluated the five algorithms with the highest accuracy, with the city and continental accuracy ranging from 85-89% to 90-94%, respectively. We then used these results to develop Cassandra, a random-forest-based classifier that identifies indicator species to aid in fingerprinting and can infer higher-order microbial interactions at each site. We further tested the Cassandra algorithm on the Tara Oceans dataset, the largest collection of marine-based microbial genomes, where it classified the oceanic sample locations with 83% accuracy. These results and code show the utility of SML methods and Cassandra to identify bioindicator species across both oceanic and urban environments, which can help guide ongoing efforts in biotracing, environmental monitoring, and microbial forensics (MF).

microbiology↗

bioRxiv2022

Cross-kingdom metagenomic profiling of Lake Hillier reveals pigment-rich polyextremophiles and wide-ranging metabolic adaptations

Background Lake Hillier is a hypersaline lake known for its distinctive bright pink color. The cause of this phenomenon in other hypersaline sites has been attributed to halophiles, Dunaliella, and Salinibacter, however, a systematic analysis of the microbial communities, their functional features, and the prevalence of pigment-producing-metabolisms has not been previously studied. Our results are evidence that Lake Hillier is composed of a diverse set of microorganisms including archaea, bacteria, algae, and viruses. Our data indicate a core microbiome in Lake Hillier composed of multiple pigment-producer microbes, many of which are cataloged as polyextremophiles. Additionally, we estimated the diversity of metabolic pathways in the lake and determined that many of these are related to pigment production. We reconstructed complete or partial genomes for 21 discrete bacteria (N = 14) and archaea (N = 7), only 2 of which could be taxonomically annotated to previously observed species. Our findings provide the first metagenomic study to decipher the source of the pink color of Australias Lake Hillier. The study of this pink hypersaline environment is evidence of a microbial consortium of pigment producers, a repertoire of polyextremophiles, a core microbiome and potentially novel species.

microbiology↗

bioRxiv2020

Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets.

molecular biology↗

bioRxiv2019

The Microbe Directory v2.0: An Expanded Database of Ecological and Phenotypical Features of Microbes.

The Microbe Directory (TMD) is a comprehensive database of annotations for microbial species collating features such as gram-stain, capsid-symmetry, resistance to antibiotics and more. This work presents a significant improvement to the original Microbe Directory (2018). This update adds 68,852 taxa, many new annotation features, an interface for the statistical analysis of microbiomes based on TMD features, and presents a portal for the broad community to add or correct entries. This update also adds curated lists of gene annotations which are useful for characterizing microbial genomes. Much of the new data in TMD is sourced from a set of databases and independent studies collating these data into a single quality controlled and curated source. This will allow researchers and clinicians to have easier access to microbial data and provide for the possibility of serendipitous discovery of otherwise unexpected trends.

microbiology↗

bioRxiv2019

Global Genetic Cartography of Urban Metagenomes andAnti-Microbial Resistance

We have created a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities across 3 years. This is the first systematic, worldwide study cataloging the urban microbial ecosystem. We identify taxonomically-defined microorganisms collected across three years. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics AMR markers, and novel genetic elements, including 10,928 viral, 1302 bacteria, and 2 archaea novel species. We identify 4,424 species of urban microorganisms and a consistent "core" of 31 species found in nearly all samples that is largely distinct from any human commensal microbiome. Profiles of AMR genes show geographic variation in type and density. Together, these results constitute a high-resolution, global metagenomic atlas, which enables the discovery of new genetic components, highlights potential forensic applications, and provides an essential first draft of the global AMR burden of the worlds cities.

microbiology↗