Welcome to the Center for BioSystems Science and Engineering. The Centre for BioSystems Science and Engineering (BSSE) at the Indian Institute of Science (IISc) was founded on June 4th, 2015, based on the critical mass that became evident due to the Interdisciplinary PhD programme in Bioengineering that started in August 2012 and a large grant from DBT entitled 'Bioengineering and Biodesign Initiative'. BSSE brings together biologists, engineering, and those who are trained as bioengineers. It is also extending its reach to medical doctors, agricultural scientists, and biomedical industries. The approach to research in BSSE is two-pronged. The first is to conduct discovery-oriented research in biology using engineering principles. This is a complementary approach that dovetails with extensive biology research being conducted in IISc. Increasing number of biologists are getting involved with BSSE. The second is to engineer biological systems, biomedical instruments, and human-assistive devices for improving human healthcare and agricultural practices. BSSE currently hosts 4 permanent faculty, 12 associate faculty, 2 INSPIRE Fellows and 32 PhD students.
The BSSE Research Symposium is our platform to showcase, deliberate and improve the research at BSSE. We take great pleasure in inviting you for the 5th BSSE Annual Research Symposium to be held on the 24th and 25th of January, 2019.
At this year's symposium we have theme based sessions to cover the entire gamut of research activities at BSSE. In the end, to discuss the way forward for the field of Bioengineering in India, we have a panel discussion with researchers from IISc, four IITs and other reputed institutions across the nation. We hope that, this 2 day symposium excites you as much as we are delighted in bringing it to you. Live stream @ mmcr2.iisc.ac.in.
Venue : MRDG Seminar Hall, 1st Floor, Biological Sciences Building, IISc. We are here.
Detailed schedule and abstracts here.
Click here to navigate our beautiful campus.
Programme, Day 1 (24th Jan.)
Sanjay K. Biswas Memorial Lecture : Multi, Inter, and Trans: Brothers from Different Mothers by Dr. Anurag Agrawal (IGIB, Delhi) on the 24th of January, 2019 at 09 30 hrs
In his own words : As a physician-scientist, I am often confronted by multi-, inter- and trans-disciplinary matters. While they superficially look similar, the genetics are very different. In my talk, we will explore how the coming together of disciplines accelerates scientific discovery, and why it is important that we recognise the inherent differences in the way this can happen. Using examples from my lab, I hope to illustrate the strengths and weaknesses of these brothers from different mothers; hopefully conveying that being prepared to cross boundaries, without preparation, is half the battle. Above everything else, I hope to share the joy of messy explorations of fields, where half of what you know is false and you don't know which half.
Biomechanics : 10 30 to 12 45 hrs
Towards Bio-Cyber Physical Systems
Biological cells sense, process information, and respond in their own right. Therefore, it is an interesting prospect to interface cells with engineered sensors and actuators using control and computation. As a small step towards that, the multidisciplinary CyberGut team in IISc is working to augment animal models for the gut-epithelium with engineered in-vitro models using gut-on-a-chip and active scaffold platforms. The other objectives of the CyberGut project are (a) to analyze the large data obtained using “cell sensors” to find hidden patterns and causative relationships using machine learning and to feed the inferences back to probe stochasticity in gut-biology; and (b) to perform genome level biological network analysis to identify regulatory proteins and then manipulate cellular responses, to pave the way for understanding and controlling gut-epithelium in a diarrheal disease condition. In this talk, ongoing work on engineering and biology aspects of the project will be discussed.
AFM Force spectroscopy for mechanical characterization of biological cell and soft sample
Present research work is focused on the development of contact models
and experimental methods for AFM force spectroscopy technique in soft material characterization,
mainly polymer gels and live biological cells. We have addressed two of the most common issues in
the analysis of nanoindentation data of soft materials. Firstly, the correction to bottom substrate
effect arising during thin sample studies and second, the contact model for simultaneous evaluation
of nonspecific adhesion property along with elasticity. The developed contact model has applications
in the characterization of soft materials showing adhesive elastic nature. The effectiveness of
improvements made in the contact models is experimentally validated by testing transversely isotropic
polymer gels of different stiffness and live MCF-7 adenocarcinoma cancer cells. Further, the developed
correction factor for finite thickness correction is incorporated into a dynamic contact model for
micro-rheological study of live cells. The model is applied to study the micro-rheology of Human
Mesenchymal stem cells and HCT-116 Colorectal cancer cells in the context of EMT (Epithelial to
Mesenchymal transformation) in cancer progression. The main advantage of the proposed model is its
closed-form expression, making it easy to use for AFM force spectroscopic data analysis. If time
permits, we will discuss some other ongoing biomechanical problems ongoing in our lab.
A non-dimensional mechanical model of the nucleus for predicting molecular mechanisms from nuclear morphology
by Dr. Sreenath Balakrishnan, BSSE
Morphology of the nucleus is an important regulator of gene-expression and therefore
of cell function. Aberrations in nuclear morphology are an indicator of cellular dysfunction and have been
used to diagnose various diseases such as cancer and laminopathies. From a biochemical perspective, changes
in nuclear morphology are due to differences in the expression of proteins such as lamins and cytoskeleton.
To obtain the molecular mechanism, these proteins are systematically probed by various experimental techniques.
On the other hand, from a mechanical perspective, the shape of the nucleus is a result of the forces acting on
the nuclear envelope and its mechanical properties. Hence, information regarding these mechanical factors is
contained in the morphology of the nucleus. Here, we present a mechanical model to decompose the contributions
of the forces and mechanical properties from the nuclear morphology and thereby indicate the molecular mechanism
responsible for changes in the shape of the nucleus.
We assumed a simplified, axisymmetric model wherein two forces act on the nuclear envelope; (i) an inflating
pressure and (ii) a compressive force from cortical actin akin to a flat plate pushing down on the nucleus.
The governing equations of mechanical equilibrium revealed that the ensuing nuclear morphology depended only
on two non-dimensional parameters; (i) the ratio between the inflating pressure and the elastic modulus of the
nuclear envelope and (ii) the ratio between the compressive force and the inflating pressure. By simulating
nuclear morphologies for a range of values of these non-dimensional parameters we predicted a relationship among
nuclear shape parameters such as projected area, surface area and volume. Individual nuclei of Huh7 and HeLa cells
were in close agreement (< 5% error) with this prediction. The aforementioned non-dimensional parameters
corresponding to individual nuclei could be obtained by fitting our model to its nuclear shape parameters.
By comparing these non-dimensional parameters between control and treated cells, we can discern the molecular
mechanism responsible for changes in nuclear morphology.
We present a case study wherein changes in nuclear mechanics due to Hepatitis C Virus (HCV) were studied using
our model. The model predicted a decrease in the elastic modulus of the nuclear envelope and an increase in
compression force from cortical actin due to HCV. These mechanical predictions further suggested down-regulation
of lamin-A,C, the major structural member of the nuclear envelope, and up-regulation of actin. Both these
predictions were experimentally verified.
In summary, we propose a novel method for obtaining the molecular mechanism responsible for changes in nuclear
mechanics by merely analysing the nuclear morphology using a quantitative model. The procedure is as follows:
Obtain the three-dimensional morphology of the nuclei of control and treated cells using confocal microscopy.
Calculate the projected area, surface area and volume of each nuclei.
Estimate the non-dimensional parameters from the nuclear shape parameters using our model.
Analyse the differences in non-dimensional parameters between control and treated cells to obtain the molecular mechanism.
Stress Fibre Growth and Remodelling Determines Cellular Morphoelastic Response under Uniaxial Cyclic Stretch
by Aritra Chatterjee, BSSE
Mechanical forces are important determinants in development, from molecular assembly of the
cell organelles to the constitution of an entire organ. The pioneering works of D’Arcy Thompson “On Growth and Form”
was essential in establishing the importance of mechanics in biological systems.Adherent fibroblasts in tissues that
undergo cyclic stretch, such as arteries and lung, are integral in determining the functional tissue response.
Application of cyclic uniaxial stretch leads to reorientation of adherent cells on substrates from random to a well-defined
and uniform angle perpendicular to the direction of stretch.The mechanistic reasons underlying active cytoskeletal
remodelling, the individual and combined roles of the cytoskeletal proteins under dynamically stretched conditions,
and their links to contractility however remain underexplored. In this study, we provide a novel growth and remodelling
framework to study the effect of uniaxial cyclic stretch in fibroblast using both using both experimental and theoretical
techniques. We show that uniaxial cyclic stretch induces lengthening and realignment in stress fibres which influences
the cellular response. Realignment of stress fibers along a uniform perpendicular to the direction of applied stretch
for prolonged duration also increases the effective elastic cell modulus. We also report significant increase in the
overall actin fluorescent intensity and cortical actin thickness in fibroblasts as well as cell elongation along the
reorientation direction under uniaxial cyclic stretch. Using cytoskeletal disruptor treatments, we further show that
microtubules do not influence in cell stiffness or reorientation changes under cyclic stretch but are important in nuclear
reorientation. Finally, based on our experimental observations we propose a biologically motivated theoretical model to
incorporate the effects of amplitude and time duration of uniaxial cyclic stretch on a single cell. Finally, the model
incorporates novel evolution equations for stress fibre growth and remodelling which, offers predictive capability in
generating cellular morphometrics sensitive to a wide range of changes in experimental inputs.
Neuroscience and Control Systems : 14 00 to 16 15 hrs
Visual similarity account of reading jumbled words
by Aakash Agrawal, BSSE
Reading speed for jumbled words is not severely impeded if we preserve its end letters. This effect is
popularly known as “Cambridge University Effect”. Various letter coding schemes fail to explain this effect. Here, we propose
that the visual properties of our brain are sufficient to account for this effect. We begin by alleviating the problem of
reading jumbled words into a visual search task. Next, we develop three models of varying complexity to understand how letters
combine to form strings and tested them on two lexical tasks. 1) Scrambled word task. 2) Lexical decision task. Interestingly,
the model can predict the time taken to solve scrambled words, and lexical decision time for non-words. It can also predict
difficulty in reading jumbled WRODS and 7EX7 W17H NUM83R5. Thereby, we hope to have cracked the orthographic code.
Learning forward predictive model with neural networks
by Saurabh Kothari, BSSE
In our day to day life, we make variety of movements like reaching for a glass of water, handling a tool,
holding a cup etc. To plan and control such movements, the brain is hypothesized to learn a forward predictive model that predicts
how the body will react to the motor commands from the brain. In other words, the brain must learn to represent the nonlinear
dynamics of body motion. To understand how the brain might do this, we are developing a biologically plausible neural network
model to learn the forward predictive model for a virtual arm. The neural network model is implemented in Nengo simulator and
the virtual arm is implemented in OpenSim.
Programme, Day 2 (25th Jan.)
Tissue Engineering and Drug Delivery : 09 30 to 12 40 hrs
Non-traditional approaches in drug delivery, diagnostics and biomaterials fabrication
A major thrust in my group is to develop technologies for infectious disease management to curb
the emerging threat of antimicrobial resistance, one of the biggest health challenges of our century. In this regard,
I will demonstrate three research approaches taken by my group, each pertaining to the broad area of drug delivery,
diagnostics and biomaterials fabrication. In the first, I will demonstrate a novel drug delivery platform to co-target
cancer and intracellular bacterial infections in cancer. We all may not know that bacteria can behave as both cancer-causative
and cancer- prevailing agents. Thus, targeting bacteria that otherwise escape antimicrobial action by host cell-localization
is important to curb secondary infections that may lead to life- threatening conditions like sepsis. Another way to manage
sepsis is through rapid and early bedside diagnosis. In the second example, I will showcase a simple and disposable point-of-care
(POC) device called SeptifloTM that can not only identify but also stratify bacterial infections based on their Gram status under
10 min from a drop of human blood. While conventional diagnostic systems rely on amplifying minute quantities of DNA or measuring
the late host response, our system works by detecting naturally amplified pathogen-associated molecular patterns that are unique
footprints of infection. The preliminary clinical results look promising as they show better performance than existing methods
for bacteremia diagnosis. Finally, I will illustrate how free-floating scaffolds of living cells can be simply and conveniently
assembled using external AC electric fields. While the 1D and 2D cellular architectures serve as biomaterial constructs, the 0D
bacterial microarrays are ideal for label-free biosensing and single cell analysis.
Disparate effects of PEG or albumin based surface modification on uptake of nano- and micro-particles
by Preeti Sharma, BSSE
Surface modification of particulate systems is a commonly employed strategy to alter their interaction with
proteins and cells. Past studies on nano-particles have shown that surface functionalization with polyethylene glycol (PEG) or
proteins such as albumin increases circulation times by reducing their phagocytic uptake. However, studies on surface functionalized
micro-particles have reported contradictory results. Here, we investigate the effects of surface functionalization using polystyrene
particles with 4 different diameters ranging from 30 nm-2.6 µm and coating them either with albumin or PEG. Our results show that
with increasing particle size, surface functionalization has less to no effect on altering phagocytic uptake. The data also suggests
that these differences are observed even with a dense arrangement of molecules on the surface (dense brush conformation for PEG
conjugation), appear to be independent of the serum proteins adsorbing on particles surfaces and is independent of the endocytic
uptake pathway. These results provide insight into the differences in the ability of surface modified nano- and micro-particles
to avoid phagocytic uptake.
Investigation of pore forming intermediates of Listeriolysin O coupled with its effect on lipid dynamics
by Ilanila I P, BSSE
Listeriolysin O (LLO) comes under the class of cholesterol dependent cytolysin (CDC)
pore-forming protein, that is secreted by a gram-positive bacterium Listeria monocytogenes. It causes
listeriosis, a fatal disease to immune-compromised individuals as well as infants. LLO assists the
bacteria, through a pH-dependent mechanism, to escape from the endocytic vesicle that is highly acidic
in nature (pH 5.5). Pore formation has been studiedand found to be initiated by the binding of
LLO to cholesterol, followed by oligomerization of the monomers and insertion of transmembrane segments
inside the bilayer to form a pore. Studies suggest that LLO transitions through an inactive intermediate
state, called a pre-pore, in the pore formation process. Although LLO has been widely studied, there is
very little information in the literature that connects the manner in which membrane lipid dynamics are
modulated during pore formation.To address some these outstanding issues pertaining to LLO interaction
and assembly on phospholipid membrane, we used fluorescence correlation spectroscopy (FCS) and FRET on
artificial membrane systems.
Magnetism in biomedicine: basics and applications
Recent developments in synthesis and applications of magnetite nanoparticles, with
negligible toxicity and favorable biodistribution, allows for reproducible control of their complex
magnetic relaxation behavior, even in “extreme” biological environments. This has enabled us to address
two of the principal challenges in biomedical nanoscience and personalized medicine, i.e. detecting disease
at the earliest possible time prior to its ability to cause damage (imaging and diagnostics) and delivering
treatment at the right place, at the right time while minimizing exposure (targeted therapy with a triggered
release). Central to this work is the size-dependent magnetic properties of nanoparticles and specifically
tailoring their Néel and Brownian relaxation dynamics in vivo to any specific applied frequency. Further,
such work requires coordinated efforts in synthesis of highly-monodisperse and phase-pure magnetite cores,
biochemical surface functionalization, biodistribution and pharmacokinetic studies, advanced characterization,
and modeling of magnetization response. Currently, our work is focused on Magnetic Particle Imaging (MPI),
and to a lesser extent on diagnostic relaxometry and hyperthermia as a potential adjuvant therapy treatment of cancer.
Magnetic Particle Imaging (MPI) is an emerging, tracer-based, whole-body medical imaging technology with high image
contrast (no tissue background) and nanogram sensitivity to an optimized tracer consisting of an iron-oxide
nanoparticle core and a biofunctionalized shell. MPI is linearly quantitative with tracer concentration, and
has zero tissue depth attenuation; it is also safe, uses no ionizing radiation and clinically approved tracers.
MPI is the first biomedical imaging technique that truly depends on nanoscale materials properties; in particular,
their response to alternating magnetic fields in a true biological environment needs to be optimized.
In this talk, I will introduce the underlying physics of MPI, the alternative approaches to image reconstruction,
and describe recent results in the development of our highly optimized and functionalized nanoparticle tracers
for MPI. I will then present state-of-the-art imaging results of preclinical in vivo MPI experiments of cardiovascular
(blood-pool) imaging, stroke , GI bleeding, and cancer using rodent models. I will also discuss a related diagnostic
method using magnetic relaxation and illustrate its use for detecting specific protease cancer markers in solution.
Overall, I will demonstrate a multidisciplinary approach that is essential to move biomedical nanomagnetics into the
next phase of innovative translational research and commercialization, emphasizing the development of quantitative
in vivo imaging, and image guided therapy including validation of delivery and therapy response
Smart Nanotextiles in Healthcare
The development of smart nanotextiles has the potential to revolutionize various realms encompassing
healthcare, sports, military applications and fashion. This is achievable either through the integration of novel
nanomaterials, fibers, coatings, etc. onto conventional textiles, or by the use of nanofabrication techniques that
provide the textile with nanoscale dimensions. Nanoscale engineering of this kind would bestow new functionalities
to the textiles including self-cleaning, sensing, drug delivery, tissue regeneration, etc. Our group has recently
developed smart nanotextiles having nanofibrous geometry from biodegradable polymers by utilizing a variant of the
conventional electrospinning process. Tunability in mechanical properties, drug release, etc was readily achieved
from these biodegradable nanotextiles fabricated from nano yarns, which are bundles of thousands of nanofibers
themselves. This talk will address the current research in the field of smart nanotextiles, from fiber manipulation
and development, to two diverse end uses in medicine, viz., drug eluting implants and vascular grafts.
Clinician and Industry talks : 14 00 to 14 50 hrs
Revolutionizing Respiratory Medicine through Biomedical Devices
The physician’s foray into the world of biomedical design dates to the early 19 th century, when Rene Theophile Hyacinthe Laennec, invented the stethoscope. The invention of this device was a necessity, as it was used as an interface between the ear and the patient’s chest to enable a ‘modest’ method of listening to heart and lung sounds! We have moved on from then to the present day to digital stethoscopes, life support machines, lab-on-a-chip, robotic surgeries, telemedicine and clinical decision support systems.
This talk will focus on discussing how medical devices have seamlessly integrated into clinical practice and aid in the diagnosis and treatment of respiratory diseases. Some of the desirable features of existing devices from an end user’s perspective will also be highlighted.
Panel discussion on the transition from Biotechnology to Bioengineering in India, 16 00 - 17 30 hrs
Contact us @ email@example.com We hope to see you at the BSSE Symposium.