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rabindra.tharu.np@gmail.com
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Initiation of lumen formation from junctions via differential actomyosin contractility regulated by dynamic recruitment of Rasip1
De novo lumen formation necessitates the precise segregation of junctional proteins from apical surfaces, yet the underlying mechanisms remain unclear. Using a zebrafish model, we develop a series of molecular reporters, photo-convertible and optogenetic tools to study the establishment of apical domains. Our study identifies Rasip1 as one of the earliest apical proteins recruited, which…
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rabindra.tharu.np@gmail.com
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The biosynthesis of the odorant 2-methylisoborneol is compartmentalized inside a protein shell
Terpenoids are the largest class of natural products, found across all domains of life. One of the most abundant bacterial terpenoids is the volatile odorant 2-methylisoborneol (2-MIB), partially responsible for the earthy smell of soil and musty taste of contaminated water. Many bacterial 2-MIB biosynthetic gene clusters were thought to encode a conserved transcription factor,…
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rabindra.tharu.np@gmail.com
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Effectiveness of BNT162b2 XBB vaccine in the US Veterans Affairs Healthcare System
Data evaluating effectiveness of XBB.1.5-adapted vaccines against JN.1-related endpoints are scarce. This nationwide test-negative case-control study within the US Veterans Affairs Healthcare System aims to estimate vaccine effectiveness (VE) of BNT162b2 XBB.1.5-adapted vaccine compared to not receiving an XBB vaccine of any kind against COVID-19 hospitalization, emergency department or urgent care visits (ED/UC), and outpatient…
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rabindra.tharu.np@gmail.com
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A long-context language model for deciphering and generating bacteriophage genomes
Inspired by the success of large language models (LLMs), we develop a long-context generative model for genomes. Our multiscale transformer model, megaDNA, is pre-trained on unannotated bacteriophage genomes with nucleotide-level tokenization. We demonstrate the foundational capabilities of our model including the prediction of essential genes, genetic variant effects, regulatory element activity and taxonomy of unannotated…
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rabindra.tharu.np@gmail.com
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A large-scale examination of inductive biases shaping high-level visual representation in brains and machines
The rapid release of high-performing computer vision models offers new potential to study the impact of different inductive biases on the emergent brain alignment of learned representations. Here, we perform controlled comparisons among a curated set of 224 diverse models to test the impact of specific model properties on visual brain predictivity – a process…
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rabindra.tharu.np@gmail.com
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Genome-wide screen of Mycobacterium tuberculosis-infected macrophages revealed GID/CTLH complex-mediated modulation of bacterial growth
The eukaryotic Glucose Induced Degradation/C-Terminal to LisH (GID/CTLH) complex is a highly conserved E3 ubiquitin ligase involved in a broad range of biological processes. However, a role of this complex in host anti-microbial defenses has not been described. We exploited Mycobacterium tuberculosis (Mtb) induced cytotoxicity in macrophages in a FACS based CRISPR genetic screen to…
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rabindra.tharu.np@gmail.com
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Ancestral neural circuits potentiate the origin of a female sexual behavior in Drosophila
Courtship interactions are remarkably diverse in form and complexity among species. How neural circuits evolve to encode new behaviors that are functionally integrated into these dynamic social interactions is unknown. Here we report a recently originated female sexual behavior in the island endemic Drosophila species D. santomea, where females signal receptivity to male courtship songs…
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rabindra.tharu.np@gmail.com
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Optogenetic dissection of transcriptional repression in a multicellular organism
Transcriptional control is fundamental to cellular function. However, despite knowing that transcription factors can repress or activate specific genes, how these functions are implemented at the molecular level has remained elusive, particularly in the endogenous context of developing animals. Here, we combine optogenetics, single-cell live-imaging, and mathematical modeling to study how a zinc-finger repressor, Knirps,…
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rabindra.tharu.np@gmail.com
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Structure, interaction and nervous connectivity of beta cell primary cilia
Primary cilia are sensory organelles present in many cell types, partaking in various signaling processes. Primary cilia of pancreatic beta cells play pivotal roles in paracrine signaling and their dysfunction is linked to diabetes. Yet, the structural basis for their functions is unclear. We present three-dimensional reconstructions of beta cell primary cilia by electron and…
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rabindra.tharu.np@gmail.com
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The origin and maintenance of supergenes contributing to ecological adaptation in Atlantic herring
Chromosomal inversions are associated with local adaptation in many species. However, questions regarding how they are formed, maintained and impact various other evolutionary processes remain elusive. Here, using a large genomic dataset of long-read and short-read sequencing, we ask these questions in one of the most abundant vertebrates on Earth, the Atlantic herring. This species…
