Research

July1

Cytoskeleton and Cell Shape (CyCelS) Lab


We combine microtubule (MT) cytoskeleton and moeculaCytoskeleton and Cell Shape Labr motors in computater simulations and in vitro reconstitution, to study collective effects that drive cell shape and division. Some current proejcts are described in detail below. For open positions refer to the tab to the right.

Collective Transport of Microtubule Asters by Molecular Motors and Self-Organized Pattern Formation
Phallusia oocyte with tubulin labels Voronoi tessellated

In recent work together with Dr. Janet Chenevert we have modelled the self-organized pattern formation of multiple microtubule (MT) asters by the interaction of the MTs with kinesin-5 like molecular motors. In an iterative manner we have demonstrated that the structures surprisingly follow the statistics of “circle packing” seen in classical geometrical systems. This problem has its origins in Gauss and Lagrange’s work on optimal packing patterns. You can read more in the Journal of Cell Science (Khetan, et al. 20021).

In vitro reconstitution of purified molecular motors and microtubules (MTs)
Gliding assays of microtubule driven by a minima S. cerevisiae dynein.

Stochastic simulations of multi-protein transport

A mathematical model based on detailed single-molecule mechanics (Jain, Khetan and Athale 2019) integrates experiment and theory.

Setup of the dynein gliding assay in simulation and experiment

Dynein Collective Transport: Simulation & Experiment (Jain et al. 2019 Soft Matter)


Simulating MT asters collective transport based on ex vivo Xenopus extract experiments (Athale et al. 2014 Phys. Biol. 11: 016008) and the in vivo self-organisation of spindles in mouse oocyes undergoing meiosis I (Khetan & Athale, 2016 PLoS Comp Biol).

Nuclear positioning by dynein in mitosis

In more recent work we have begun to examine how these number-dependent effects affect the transport and positioning of nuclei in the budding yeast S. cerevisiae.

Mathematical modeling of cytoskeletal basis of neuronal growth cone turning to examine the limits of sensing of the MT system in axonal growth cones (Mahajan and Athale 2012).

Spindle segregation during embryonic division of the nematode Caenorhabditis elegans- In collaboration with the lab of Prof. Marie Delattre, Plasticity and Evolution of Cell Division Lab at ENS Lyon.

Tubulin Polymerization Kinetics and Dynamics
Schematic depicting the scale of MTs and kinetics of polymerization and depolymerization

MT size and kinetics of polymerization (Athale, C.A. 2011, Modelling the Spatial Pattern Forming Modules in Mitotic Spindle Assembly)

The diversity of microtubule (MT) inhibitors that originates from plants and have medicinal uses has fascinated us. We have together with our collaborators Prof. Uma Shaanker’s group in UAS Bangalore, begun to investigate the role of MT polymerization kinetics in presence of colchicine – both produced from the plant and present in the insect that feeds on it.

Quantitative Microscopy: Imaging Analysis and BigData Analytics
Increasingly we find the large datasets that were previously restricted to DNA, RNA and Protein data (genomics, transcriptomics and proteomics) have spread to image-data. These coming from High Content Screening (HCS) for genetic and drug discovery have the potential to “discover” not just sequence and structure, but functional relations between proteins in the context of spindle assembly and cell polarization. Our ambitions in this part of our lab is to build data pipelines to feed into our theoretical models and even use AI tools to Discover biology from the data alone. Some new work in the lab in collaboration with an Evolutionary Developmental Biologist (Dr. Marie Delattre, ENS Lyon, France) is in preliminary stages. Watch this stage for more.

Image of the GUI screen of DIC object tracking program

The GUI of the DIC object tracking (DICOT) program. This is part of a publication by Chaphalkar*, Jawale*, Khatri and CAA 2021 Biophy J. (* equal contribution)

TOOLS: MATLAB, ImageProcessing and Deep learning toolbox, SciPy, Python image analysis libraries, DL libraries.

Image from the report by Chaphalkar et al.

Amtrak used to quantify E. coli nucleoids

Mathematical Modeling of Pattern Formation

Schematic of models of receptor mobility diffusion and dimerization, REF: Deshpande et al. (2017) Phys. Biol.

Receptor aggregation dynamics by dimerization is thought to be critical for signalling in cancer cells, as summarized in a theoretical model by us in 2005 (Athale, Mansury & Deisboeck J. Theor. Biol.). The microscopic details of such receptor dynamics have been more recently modeled using coarse-grained simulations in collaboration with the Biophysical Chemistry lab in NCL Pune (Pawar et al. 2014, Sengupta et al. 2016). We have more recently developed a Monte-Carlo simulation of receptor dimerization kinetics based on a diffusion and aggregation model in a heterogenous environment (Deshpande et al. (2017) Phys. Biol).

Bacterial Cell Size Biophysics
Image from Gangan & Athale (2017) of microfluidics of E. coli cells grown in LB at 37 deg C

Constitutive GFP expressing E. coli in a "mother machine" microfluidics chip.

The cell size variability in cell shape in a population (Athale &Chaudhari Bioinformatics) is thought to be linked to replication processivity linking the rate of growth of single cells to cell division (Gangan & Athale 2017 Roy. Soc. open science). We are currently working on formalizing our insights in the form of a theoretical model using an Agent-Based Modeling (ABM) approach.

ABM for tumour growth: network model from Zhang, Athale & Deisboeck (2007) J. Theor. Biol.

ABMs: Discrete models related to cellular automata, but more flexible  for rule-based behavior.

Self-Organized Collective Behaviour

Self-organization of aster patterns by mechanics (Khetan & Athale, in press)

As with flocks of birds, schooling of fish and people milling at a railway station, collective patterns that emerge have fascinated humankind since time immemorial. We hope to work on biomolecules and find out the laws by which they organize. Finding the similarities and differences to more complex pattern, is our way of working our way upwards in complexity, in the hope of finding out the universal laws and the exceptions that guide such patterns. The 1974 parable from Films Division India “एक, अनेक और एकता”, a must watch.

The Films Division Documentary on unity of purpose

Collective effects self-organized: in a social context (Films Division India): This social parable from Films Division India (1974) has amazing parallels in collective behaviour as we think of it- birds swarming, people at a railway station, fish schooling.

Funding

  1. Indo French Centre for the Promotion of Advanced Research (CEFIPRA)

    CEFIPRA Logo

    CEFIPRA: Indo French Agency for Promotion of Advanced Research

  2. Department of Science and Technology, Govt. of India
    SERB DST
  3. Private companies for some short term projects with BS-MS undergraduate students (iGEM)
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