Biology subjects

Goyal, S.

Publications and source records attributed to Goyal, S..

3 recordsLinked to original sources

bioRxiv2018

Oscillatory cortical forces promote three dimensional cell intercalations that shape the mandibular arch

Multiple vertebrate embryonic structures such as organ primordia are composed of a volume of confluent cells. Although mechanisms that shape tissue sheets are increasingly understood, those which shape a volume of cells remain obscure. Here we show 3D mesenchymal cell intercalations, rather than cell divisions and biophysical tissue properties, are essential to shape the mandibular arch of the mouse embryo. Using a genetically encoded vinculin tension sensor, we show that cortical force oscillations promote these intercalations. Genetic loss and gain of function approaches show that Wnt5a functions as a spatial cue to coordinate cell polarity with cytoskeletal oscillation. YAP/TAZ and PIEZO1 serve as downstream effectors of Wnt5a-mediated actomyosin bias and cytosolic calcium transients, respectively, to ensure appropriate tissue form during growth. Our data support oriented 3D cell neighbour exchange as a conserved mechanism driving volumetric morphogenesis.

developmental biology↗

bioRxiv2017

Bioty: A cloud-based development toolkit for programming experiments and interactive applications with living cells

Recent advancements in life-science instrumentation and automation enable entirely new modes of human interaction with microbiological processes and corresponding applications for science and education through biology cloud labs. A critical barrier for remote life-science experimentation is the absence of suitable abstractions and interfaces for programming living matter. To this end we conceptualize a programming paradigm that provides stimulus control functions and sensor control functions for realtime manipulation of biological (physical) matter. Additionally, a simulation mode facilitates higher user throughput, program debugging, and biophysical modeling. To evaluate this paradigm, we implemented a JavaScript-based web toolkit, Bioty, that supports realtime interaction with swarms of phototactic Euglena cells hosted on a cloud lab. Studies with remote users demonstrate that individuals with little to no biology knowledge and intermediate programming knowledge were able to successfully create and use scientific applications and games. This work informs the design of programming environments for controlling living matter in general and lowers the access barriers to biology experimentation for professional and citizen scientists, learners, and the lay public.\n\nSignificance StatementBiology cloud labs are an emerging approach to lower access barriers to life-science experimentation. However, suitable programming approaches and user interfaces are lacking, especially ones that enable the interaction with the living matter itself - not just the control of equipment. Here we present and implement a corresponding programming paradigm for realtime interactive applications with remotely housed biological systems, and which is accessible and useful for scientists, programmers and lay people alike. Our user studies show that scientists and non-scientists are able to rapidly develop a variety of applications, such as interactive biophysics experiments and games. This paradigm has the potential to make first-hand experiences with biology accessible to all of society and to accelerate the rate of scientific discovery.

bioengineering↗

bioRxiv2017

NMDA-receptor antibodies alter cortical microcircuit dynamics

NMDA-receptor antibodies (NMDAR-Ab) cause an autoimmune encephalitis with a diverse range of electroencephalographic (EEG) abnormalities. NMDAR-Ab are believed to disrupt receptor function, but how blocking this excitatory neurotransmitter can lead to paroxysmal EEG abnormalities - or even seizures - is poorly understood. Here, we show that NMDAR-Ab change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity, and predispose to paroxysmal EEG abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in paediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab- related changes render microcircuitry critically susceptible to overt EEG paroxysms, when these key parameters are changed. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.

neuroscience↗