Biology subjects

Dasgupta, I.

Publications and source records attributed to Dasgupta, I..

8 recordsLinked to original sources

bioRxiv2025

Bile Salts and Bacterial Bile Salt Hydrolase Activity Differentially Influence Escherichia coli Colonization and FXR Signaling in Colorectal Cancer Organoids

Bile salts are key regulators of host-microbe interactions and epithelial signaling in the intestine. Gut bacteria can deconjugate primary bile salts, which can be leveraged to engineer targeted therapies through bile salt hydrolase (BSH) activity. However, the interplay between bile salt signaling, microbial metabolism, and tumor-associated colonization remains poorly understood. Here, we establish an in vitro colon organoid platform to dissect bile salt-driven epithelial-microbe dynamics at cellular resolution. Using this system, we found that bile salts markedly modulated colonization of native Escherichia coli (EcAZ-2) and a BSH-expressing strain (EcAZ-2LsBSH) in healthy versus tumor murine organoids. Under bile salt exposure, EcAZ-2LsBSH preferentially colonized tumor organoids, though overall colonization was lower than that of the non-BSH strain. Beyond effects on bacterial colonization, bile salts also directly activated host signaling pathways. In presence of bile salts, EcAZ-2LsBSH significantly enhanced activation of bile acid receptors such as farnesoid X receptor (FXR) by 2-fold in healthy organoids. These findings reveal a mechanistic bridge between in vivo microbial function and bile salt interactions, offering potential microbiota and bile acid targeted therapeutic strategies.

cancer biology↗

bioRxiv2023

The ability of the LIMD1 and TRIP6 LIM domains to bind to f-actin under strain is critical for their tension dependent localization to adherens junctions and association with the Hippo pathway kinase LATS1.

A key step in regulation of Hippo pathway signaling in response to mechanical tension is recruitment of the LIM domain proteins TRIP6 and LIMD1 to adherens junctions. Mechanical tension also triggers TRIP6 and LIMD1 to bind and inhibit the Hippo pathway kinase LATS1. How TRIP6 and LIMD1 are recruited to adherens junctions in response to tension is not clear, but previous studies suggested that they could be regulated by the known mechanosensory proteins -catenin and vinculin at adherens junctions. We found that the three LIM domains of TRIP6 and LIMD1 are necessary and sufficient for tension-dependent localization to adherens junctions. The LIM domains of TRIP6, LIMD1, and certain other LIM domain proteins have been shown to bind to actin networks under strain/tension. Consistent with this, we show that TRIP6 and LIMD1 colocalize with the ends of actin fibers at adherens junctions. Point mutations in a key conserved residue in each LIM domain that are predicted to impair binding to f-actin under strain inhibits TRIP6 and LIMD1 localization to adherens junctions and their ability to bind to and recruit LATS1 to adherens junctions. Together these results show that the ability of TRIP6 and LIMD1 to bind to strained actin underlies their ability to localize to adherens junctions and regulate LATS1 in response to mechanical tension.

cell biology↗

bioRxiv2023

A geminivirus AC5 protein interacts with plant hormonal signalling and impacts plant defence

Geminiviruses are a large group of plant viruses responsible for yield loss in various crops, mainly in the tropical and sub-tropical regions. Geminiviruses encode six to nine multifunctional proteins, which interact with plant components to cause pathogenesis. One of the least studied geminiviral proteins is AC5. This study presents the first evidence of an AC5 protein interacting with a component of the abscisic acid signalling pathway, resulting in a depressed state. We show that the AC5 protein, encoded by Sri Lankan cassava mosaic virus is important for symptom development and virus accumulation in the experimental host Nicotiana benthamiana. The above interaction perturbs the abscisic acid signalling pathways, leading to compromised expression of defense-related genes and insensitivity to abscisic acid in transgenic Arabidopsis plants. This suggests a novel role of AC5 to facilitate virus propagation. Furthermore, we show that transiently suppressing the expression in N. benthamiana PP2C with which AC5 interacts, results in a reduction in viral titers possibly due to augmented ABA signaling and its defense-related roles. This research provides valuable insights into how geminiviral proteins manipulate ABA-mediated defence pathways, paving the way for further investigation into the underlying mechanisms and potential applications in plant protection against viral infections.

plant biology↗

bioRxiv2019

A theory of learning to infer

Bayesian theories of cognition assume that people can integrate probabilities rationally. However, several empirical findings contradict this proposition: human probabilistic inferences are prone to systematic deviations from optimality. Puzzlingly, these deviations sometimes go in opposite directions. Whereas some studies suggest that people under-react to prior probabilities (base rate neglect), other studies find that people under-react to the likelihood of the data (conservatism). We argue that these deviations arise because the human brain does not rely solely on a general-purpose mechanism for approximating Bayesian inference that is invariant across queries. Instead, the brain is equipped with a recognition model that maps queries to probability distributions. The parameters of this recognition model are optimized to get the output as close as possible, on average, to the true posterior. Because of our limited computational resources, the recognition model will allocate its resources so as to be more accurate for high probability queries than for low probability queries. By adapting to the query distribution, the recognition model \"learns to infer.\" We show that this theory can explain why and when people under-react to the data or the prior, and a new experiment demonstrates that these two forms of under-reaction can be systematically controlled by manipulating the query distribution. The theory also explains a range of related phenomena: memory effects, belief bias, and the structure of response variability in probabilistic reasoning. We also discuss how the theory can be integrated with prior sampling-based accounts of approximate inference.

animal behavior and cognition↗

bioRxiv2018

Learning to act by integrating mental simulations and physical experiments

People can learn about the effects of their actions either by performing physical experiments or by running mental simulations. Physical experiments are reliable but risky; mental simulations are unreliable but safe. We investigate how people negotiate the balance between these strategies. Participants attempted to shoot a ball at a target, and could pay to take practice shots (physical experiments). They could also simply think (run mental simulations), but were incentivized to act quickly by paying for time. We demonstrate that the amount of thinking time and physical experiments is sensitive to trial characteristics in a way that is consistent with a model that integrates information across simulation and experimentation and decides online when to perform each.

animal behavior and cognition↗

bioRxiv2017

Remembrance of Inferences Past

Bayesian models of cognition assume that people compute probability distributions over hypotheses. However, the required computations are frequently intractable or prohibitively expensive. Since people often encounter many closely related distributions, selective reuse of computations (amortized inference) is a computationally efficient use of the brains limited resources. We present three experiments that provide evidence for amortization in human probabilistic reasoning. When sequentially answering two related queries about natural scenes, participants responses to the second query systematically depend on the structure of the first query. This influence is sensitive to the content of the queries, only appearing when the queries are related. Using a cognitive load manipulation, we find evidence that people amortize summary statistics of previous inferences, rather than storing the entire distribution. These findings support the view that the brain trades off accuracy and computational cost, to make efficient use of its limited cognitive resources to approximate probabilistic inference.

animal behavior and cognition↗

bioRxiv2017

TRIP6 inhibits the Hippo signaling pathway in response to tension at adherens junctions

The transcriptional co-activator YAP controls cell proliferation, survival, and tissue regeneration in response to changes in the mechanical environment. It is not known how mechanical stimuli such as tension are sensed and how the signal is transduced to control YAP activity. Here we show that the LIM domain protein TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to promote YAP activity by inhibiting the LATS1/2 kinases. Previous studies showed that vinculin at adherens junctions becomes activated by mechanical tension. We show that vinculin inhibits Hippo signaling by recruiting TRIP6 to adherens junctions and stimulating its binding to and inhibition of LATS1/2 in response to tension. TRIP6 competes with MOB1 for binding to LATS1/2 thereby blocking MOB1 from recruiting the LATS1/2 activating kinases MST1/2. Together these findings reveal a novel mechanotransduction cascade that transduces tension signals sensed at adherens junctions to control Hippo pathway signaling.

cell biology↗

bioRxiv2017

Amortized Hypothesis Generation

Bayesian models of cognition posit that people compute probability distributions over hypotheses, possibly by constructing a sample-based approximation. Since people encounter many closely related distributions, a computationally efficient strategy is to selectively reuse computations - either the samples themselves or some summary statistic. We refer to these reuse strategies as amortized inference. In two experiments, we present evidence consistent with amortization. When sequentially answering two related queries about natural scenes, we show that answers to the second query vary systematically depending on the structure of the first query. Using a cognitive load manipulation, we find evidence that people cache summary statistics rather than raw sample sets. These results enrich our notions of how the brain approximates probabilistic inference.

animal behavior and cognition↗