Biology subjects

Kumaran, D.

Publications and source records attributed to Kumaran, D..

6 recordsLinked to original sources

bioRxiv2024

Iron deprivation activates aboveground cell wall biosynthesis in Populus and the role of PtrbHLH011

Lack of mechanistic understanding of the environmental plasticity of secondary cell wall (SCW) biosynthesis hinders the massive bioenergy production on marginal lands. Growing bioenergy crops on marginal lands is appealing to minimize competition for arable land. However, abiotic stresses, particularly iron deficiency stress, are widespread to perturb SCW biosynthesis. In poplar, a major bioenergy crop, we demonstrated that iron deprivation activates stem SCW biosynthesis and identified transcription factor PtrbHLH011 as a possible underlying regulator. PtrbHLH011 is a potent repressor of SCW, whose overexpression resulted in a reduction of stem SCW by over 65%. Our genomic and molecular studies discovered that PtrbHLH011 binds to the AAAGACA sequence and represses essential genes for SCW biosynthesis, flavonoid biosynthesis, and iron homeostasis. Wood formation and iron deprivation downregulates PtrbHLH011 to release the transcriptional repression. Our findings reveal a regulatory mechanism coordinating SCW biosynthesis in response to environmental iron availability and suggest that PtrbHLH011 manipulation may help engineer bioenergy crops with improved performance under marginal conditions.

plant biology↗

bioRxiv2021

The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (Mpro)

The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or Mpro, is a promising target for development of novel antiviral therapeutics. Previous X-ray crystal structures of Mpro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded Mpro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these datasets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a temperature-dependent conformational landscape for Mpro, including mobile solvent interleaved between the catalytic dyad, mercurial conformational heterogeneity in a key substrate-binding loop, and a far-reaching intramolecular network bridging the active site and dimer interface. Our results may inspire new strategies for antiviral drug development to counter-punch COVID-19 and combat future coronavirus pandemics. SynopsisX-ray crystallography at variable temperature for SARS-CoV-2 Mpro reveals a complex conformational landscape, including mobile solvent at the catalytic dyad, mercurial conformational heterogeneity in a key substrate-binding loop, and an intramolecular network bridging the active site and dimer interface.

biophysics↗

bioRxiv2020

The Spatial Memory Pipeline: a model of egocentric to allocentric understanding in mammalian brains

In the mammalian brain, allocentric representations support efficient self-location and flexible navigation. A number of distinct populations of these spatial responses have been identified but no unified function has been shown to account for their emergence. Here we developed a network, trained with a simple predictive objective, that was capable of mapping egocentric information into an allocentric spatial reference frame. The prediction of visual inputs was sufficient to drive the appearance of spatial representations resembling those observed in rodents: head direction, boundary vector, and place cells, along with the recently discovered egocentric boundary cells, suggesting predictive coding as a principle for their emergence in animals. Strikingly, the network learned a solution for head direction tracking and stabilisation convergent with known biological connectivity. Moreover, like mammalian representations, responses were robust to environmental manipulations, including exposure to novel settings. In contrast to existing reinforcement learning approaches, agents equipped with this network were able to flexibly reuse learnt behaviours --adapting rapidly to unfamiliar environments. Thus, our results indicate that these representations, derived from a simple egocentric predictive framework, form an efficient basis-set for cognitive mapping.

neuroscience↗

bioRxiv2018

Neural signatures of detours, shortcuts and back-tracking during navigation

Central to the concept of the cognitive map is that it confers behavioural flexibility, allowing animals to take efficient detours, exploit shortcuts and realise the need to back-track rather than persevere on a poorly chosen route. The neural underpinnings of such naturalistic and flexible behaviour remain unclear. During fMRI we tested human subjects on their ability to navigate to a set of goal locations in a virtual desert island riven by lava, which occasionally shifted to block selected paths (necessitating detours) or receded to open new paths (affording shortcuts). We found that during self-initiated back-tracking, activity increased in frontal regions and the dorsal anterior cingulate cortex, while activity in regions associated with the core default-mode network was suppressed. Detours activated a network of frontal regions compared to shortcuts. Activity in right dorsolateral prefrontal cortex specifically increased when participants encountered new plausible shortcuts but which in fact added to the path (false shortcuts). These results help inform current models as to how the brain supports navigation and planning in dynamic environments.\n\nSignificance StatementAdaptation to change is important for survival. Although real-world spatial environments are prone to continual change, little is known about how the brain supports navigation in dynamic environments where flexible adjustments to route plans are needed. Here, we used fMRI to examine the brain activity elicited when humans took forced detours, identified shortcuts and spontaneously back-tracked along their recent path. Both externally and internally generated changes in the route activated the fronto-parietal attention network, whereas only internally generated changes generated increased activity in the dorsal anterior cingulate cortex with a concomitant disengagement in regions associated with the default-mode network. The results provide new insights into how the brain plans and re-plans in the face of a changing environment.

neuroscience↗

bioRxiv2018

Spotting the path that leads nowhere: Modulation of human theta and alpha oscillations induced by trajectory changes during navigation

The capacity to take efficient detours and exploit novel shortcuts during navigation is thought to be supported by a cognitive map of the environment. Despite advances in understanding the neural basis of the cognitive map, little is known about the neural dynamics associated with detours and shortcuts. Here, we recorded magnetoencephalography from humans as they navigated a virtual desert island riven by shifting lava flows. The task probed their ability to take efficient detours and shortcuts to remembered goals. We report modulation in event-related fields and theta power as participants identified real shortcuts and differentiated these from false shortcuts that led along suboptimal paths. Additionally, we found that a decrease in alpha power preceded back-tracking where participants spontaneously turned back along a previous path. These findings help advance our understanding of the fine-grained temporal dynamics of human brain activity during navigation and support the development of models of brain networks that support navigation.

neuroscience↗

bioRxiv2018

Prefrontal cortex as a meta-reinforcement learning system

Over the past twenty years, neuroscience research on reward-based learning has converged on a canonical model, under which the neurotransmitter dopamine stamps in associations between situations, actions and rewards by modulating the strength of synaptic connections between neurons. However, a growing number of recent findings have placed this standard model under strain. In the present work, we draw on recent advances in artificial intelligence to introduce a new theory of reward-based learning. Here, the dopamine system trains another part of the brain, the prefrontal cortex, to operate as its own free-standing learning system. This new perspective accommodates the findings that motivated the standard model, but also deals gracefully with a wider range of observations, providing a fresh foundation for future research.

neuroscience↗