Download Correlation between molecular biology and mechanics in liver cells

Correlation between molecular biology and
mechanics in liver cells with viral infections
G.K. Ananthasuresh
Professor
Dept. of Mechanical Engineering
Indian Institute of Science
Bangalore, India
[email protected]
Saumitra Das
Professor
Dept. of Microbiology and Cell Biology
Indian Institute of Science
Bangalore, India
[email protected]
Both professors are associated with BioSystems Science and Engineering (BSSE) and
have collaborated and co-advised a BSSE PhD student for five years.
Hepatitis C is a serious disease that has no complete cure as yet.
We want to explore mechano-biology approaches for basic understanding and
for developing novel mechanics-based diagnosis and treatment techniques. HCV-lifecycle
Journal of Virology (2008) 82 (23), p11927-38
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Mondal, Upasana Ray, Asit Manna, Romi Gupta , Swagata Roy, Siddhartha Roy, Saumitra Das 1Tanmoy
Microbiology
Mechanics
Connecting mechanics and microbiology
Interventions
Measurements
Engineering culture
techniques to create invivo like conditions:
Perfusion bioreactors
Scaffolds of tunable
stiffness and actuation.
Measuring mechanical
response:
Forces, displacements,
stiffness, viscoelasticity, etc.
Modeling and
computation.
Biological
manipulation:
Transfection,
transformation,
inducing infections.
Measuring biological
response:
Cell sensors
Gene and protein
expression
Drug efficacy
Accomplishments of the
Ananthasuresh-Das collaboration
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Miniature perfusion-bioreactors
Bio-micro-manipulation
Stiffness measurement
Inverse problems to estimate interior
properties
Active scaffolds
High-resolution imaging of cells and
organelle during culture.
Effect of viral infection on the organelles
of liver cells including their morphology,
permeability, and rigidity.
Effect of mechanical stimuli and
responses on the gene expression.
Micromanipulation station
An objective
•  Microfluidic platform for in-vivo culture
of hepatocytes to study the effects of
chronic Hepatitis C Virus infection Most studies of HCV have focussed on short term infection (2-3 days) in traditional Petri
dish cultures. But HCV is a chronic infection and it takes years for the disease to
manifest itself. The primary reason for short term studies is because of the unavailability
of platforms for in-vivo like long term cultures for hepatocytes and the difficulty of
designing, validating and standardizing such systems. This project aims at making a
platform which mimics the organisation of cells in the liver. The important aspects of
liver physiology like multiple cell types – hepatocytes, endothelial and Kupfer cells, and
shear stress due to flow will be realised on the platform. This platform will be used to
study the long-term effects of HCV infection on hepatocytes.
The platform will contain micro-fabricated structures (mostly for the flow channels) and
different cell types will be paZerned on the micro-fabricated structures to obtain the
liver sinusoids. The cells will be grown under constant flow of the culture medium. The
platform will be established as a viable, long – term, in-vivo like system of the liver invitro. Further many liver diseases such as drug induced hepatitis and viral hepatitis can
be studied using this platform to understand the mechanism of disease progression.
An alternate objective
•  Mechano-biology of hepatocytes in the
context of HCV infection
Changes in chromatin organisation and gene expression due to the alteration
in nuclear mechanics induced by HCV infection. The changes in chromatin
organisation due to the reduction of stiffness of the nuclei in HCV infection
will be studied. The changes in chromatin organisation under mechanical
stimuli – shear stress due to flow, and stretching and stiffening of the
substrate will be explored.
Required background
•  Strong expertise either in mechanics or
microbiology with conviction to learn the
other field (adequate training will be
provided).
•  Modeling skills and adequate familiarity
with engineering mathematics (or will to
acquire them).
•  Inclination towards interdisciplinary
research.
Further reading
•  S. Balakrishnan, M. S. Suma, S. R. Raju, S. D. B. Bhargav, S. Arunima,
S. Das and G. K. Ananthasuresh, "A Scalable Perfusion Culture
System with Miniature Peristaltic Pumps for Live-Cell Imaging
Assays with Provision for Microfabricated Scaffolds", BioResearch
Open Access, 2015, 4(1), 343–357. DOI: 10.1089/biores.2015.0024 •  hZp://mcbl.iisc.ernet.in/Saumitra
•  hZp://www.mecheng.iisc.ernet.in/~suresh