CONFERENCE
ON
DNA PHYSICS 2017
(9-11 March, 2017)
Programme and Abstracts
Department of Physics
Birla Institute of Technology & Science, Pilani Pilani Campus, Rajasthan (India)
Chief Patron
Prof. Souvik Bhattacharyya
Vice-Chancellor,
Birla Institute of Technology & Science, Pilani
Patron
Prof. A.K. Sarkar
Director,
Birla Institute of Technology & Science, Pilani,
Pilani Campus
Chair
Prof. Anshuman Dalvi
Head, Department of Physics
Convener
Dr. Navin Singh
Co-conveners
Dr. J.N. Bandyopadhyay
Prof. R.K. Gupta
ADVISORS TO THE ORGANIZING TEAM
Marco Zoli, University of Camerino, Italy
Gautum Menon,
Institute of Mathematical Sciences, India
Pankaj Mishra, Indian School of Mines, India
Flavio Seno, University of Padova, Italy
Debaprasad Giri, IIT-BHU, Varanasi, India
Gerald Weber,
Federal University of Mina Gerais, Brazil
Ralf Metzler, University of Potsdam, Germany
Local Organizing Team
Student’s support
Amol Holkundkar
Biswanath Layek
Debashis Bandyopadhyay
Debi Dutt Pant
Kaushar Vaidya
Kusum Lata
Madhukar Mishra
Manjuladevi V
Niladri Sarkar
R.R. Mishra
Rakesh Choubisa
Rishikesh Vaidya
Sindhu S
Srijata Dey
S.N. Karbelkar
Subhashis Gangopadhyay
Tapomay Guha Sarkar
Aditi
Arghya
Captain
Dinachandra
Ishaan
Neelakshi
Prachi
Pradeep
Parul
Rajeev
Ritika
Shivani
Sumita
Tridev
Office Staff
Shrikant Sharma
Rajeev Gaur
Virendra Yadav
SPONSORS: CSIR, DST-SERB, DRDO, DST (Rajasthan)
2
From Convener’s desk
It gives me immense pleasure to welcome all in the conference DNA Physics 2017. DNA is known to
be the molecule of life. It contains code of our life and is known to be one of the very complex as well
as interesting molecule. Researchers around the globe, regardless of their categorization as biologists,
microbiologists, physicists, engineers etc, are putting lot of efforts to understand the complex structure
and behaviour of this spectacular molecule. All are busy to unravel the secrets lying beneath the basis of
genetic code and its possible applications.
The essential aim of this conference is to bring together all the researhers whose focus is revolving
around the DNA molecule; be it fundemental or application research. On behalf of the organzing team
of the conference I sincerely hope that this conference will be immensely helpful in advancing the
existing knowledge and will lead to unravelling of further dimensions in this field. Personally, I would like to thank all the members of Department of Physics and the members of Pilani
campus who put their sincere support in organizing this event. At the end, the financial support from
CSIR, DST­SERB, DST (Rajasthan), DRDO, New Delhi, India are gratefully acknowledged.
Navin Singh
(Convener, DNA Physics 2017)
3
I Day (09-03-2017) (Thursday)
8.30 AM – 9.00 AM
Registration
9:00 – 9:30A M
Ina ugura ti on
9:30 – 10:00 A M
Tea & Photo
SESSION – I
Chair: Y. Singh
10:00 – 10:45 AM
S.M. Bhattacharjee
10:45 – 11:30 AM
Hermann Gaub
11:30 – 12:00 Noon
G.V. Soni
12:00 – 12:30 PM
R. Chakrabarti
12:30 – 12:55 PM
D. Das
1:00 – 2:30
Lunch
SESSION – II
Chair: H. Gaub
2:30 – 3:00 PM
P. Ranjith
3:00 – 3:30 PM
P.K. Mishra
3:30 – 3:50 PM
Tea
SESSION – III
Chair: R. Kapri
G. Mishra
3:50 – 4:20 PM
4:20 – 4:40 PM
Apratim Chatterji
4:40 – 5:00 PM
Abhijit Ghosh
Conference dinner at VFA ST a t 8:00 PM
II Day (10-03-2017) (Friday)
SESSION – IV
Chair: S.M. Bhattacharjee
9:00 – 9:45 AM
S. Kumar
9:45 – 10:30 AM
M. Peyrard
10:30 – 10:45 A M
Tea
SESSION – V
Chair: M. Peyrard
10:45 – 11:15 AM
Y. Singh
11:15 – 11:45 AM
Rajeev Kapri
11:45 – 12:15 PM
S. Jalan
12:15 – 12:35 PM
J. Maji
12:35 – 1:00 PM
Ajay Agarawal
1:00 – 2:30 PM
Lunch
SESSION – VI
C hair: S. Kumar
2:30 – 3:00 PM
A. Sain
3:00 – 3:20 PM
P. Debnath
3:20 – 3:40 PM
M. Suman Kalyan
Himanshu Joshi
3:40 – 4:00 PM
4:00 – 5:30 PM
Te a & Poster
Visit to Sarswati Temple
6:00 – 7:00 PM
Di nne r a t 8:00 PM in VFA ST
I I I Day (11-03-2017) (S at u rd ay )
S ES S I ON – VI I
C h air : A. S ain
9:00 – 9:30 AM
A.N. Gupta
9:30 – 10:00 AM
Alok Shah
10:00 – 10:20 AM
Rajdeep Choudhury
10:20 – 10:35 A M
Te a
S ES S I ON – VI I I
C h air : S . J alan
10:35 – 10:55 AM
Rajesh Mehrotra
10:55 – 11:15 AM
Ashok Garai
11:15 – 11:30 AM
Concluding Remarks
12:30 PM Lunch
INVITED AND
CONTRIBUTORY
TALKS
Perturbing DNA near its melting point
Somendra M Bhattacharjee
Institute of Physics, Bhubaneswar, India
Two different perturbations, force and a third strand, near the melting point of a double stranded DNA
will be considered in this talk. We show how a thermodynamic hypothesis provides the nature of the
force induced unzipping phase boundary near the melting point. We then discuss the role of bubble
fluctuations in establishing a long range attraction that leads to the state of three chain bound state when
no two are bound, a thermal analogue of the quantum Efimov effect.
1
DNA as molecular force sensor
H.E Gaub
Lehrstuhl für Angewandte Physik und Center for NanoScience,
Ludwig­Maximilians­Universität Amalienstr. 54 80799 München, Germany
The rapid development of scanned probe technologies allowing the precise application and measurement
of minute forces has opened exciting new perspectives in bio­analytics. Interactions of DNA with other
poly­nucleotides, with proteins and also small ligandscould be measured with unparalleled precision.
However, the wide spread use of AFM­based bio­analytics is hampered by the limited throughput. We
developed DNA­based molecular force balances as an alternative approach to measure the unbinding
force of inter­molecular bonds in a differential format by comparison with a known reference bond. In
addition to a marked increase in sensitivity and force resolution, this new approach allows for a parallel
assay format, which is a prerequisite for most bioanalytical applications.
The second block of this presentation will focus on the use of DNA as a programmable nano­tool.
Bottom up assembly of functional molecular ensembles with novel properties emerging from
composition and arrangement of its constituents is a prime goal of nanotechnology. With the
development of Single­Molecule Cut­and­Paste (SMC & P) we provided a platform technology for the
assembly of biomolecules at surfaces.It combines the Å positioning precision of the AFM with the
selectivity of DNA hybridization to pick individual molecules from a depot chip and allows to arrange
them on a construction site one by one. Anchors and handles are typically composed of DNA, but
alternatively a broad range of ligand­receptor systems may be employed.
2
Nucleotide and Nucleo­protein Complexes detection using Nanopore platform
Gautam V. Soni
Raman Research Institute, Bangalore 560080, India
Structure ­ Function relationship is ubiquitous in almost all of the nature's self­assembled systems. I will
introduce nanopore biophysics and its biosensing capabilities for studying structural heterogeneities in
biological systems. Spanning applications from technology to biology, I will first present my work on
developing nanopore­based novel DNA sequencing technology. This combines ultrafast single molecule
fluorescence microscopy to nanopore mesaurements to read out DNA sequence. In the second part of
my talk, I will show first ever application of solid­state nanopores in screening structural states of
nucleosomes and chromatin. Finally, I will show the new type of nanopore devices that we have built in
our lab and preliminary single molecule detection using them.
3
Probing the Dynamics of Nucleic acids in Presence of Carbon­Based Nanostructures
Soumadwip Ghosh and Rajarshi Chakrabarti
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai – 400076, India
The hybrids formed between single stranded DNA (ssDNA) and single walled carbon nanotubes
(SWCNT) are promising candidates for gene delivery vehicles. Using atomistic molecular dynamics
(MD) simulations we show that ssDNA wraps helically around the rigid SWCNT at low NaCl
concentration of the medium whereas at high salt concentration the binding gets weakened significantly
[1]. This is because of the fact that flexible ssDNA adopts a compact coil­like state at higher salt
concentration where the nucleobases undergoes self­stacking and their affinity for the CNT sidewall
decreases. This is in good agreement with the divalent salt assisted structural collapse of the ssDNA
where a significant conformational transition from the collapsed to a re­expanded one is observed due to
overcharging at a higher concentration of MgCl2 [2]. Our simulations help understanding the
destabilization of the ssDNA­SWCNT hybrids and the ultimate detachment of the substrate from the
carrier inside the cell membrane for a successful gene delivery process [3]. Duplex nucleic acids, on the
other hand, are structurally more rigid than the single stranded ones. Apart from their ability to
accommodate small metal/molecular ions into their various binding sites [4], artificial duplex nucleic
acids can be useful for antisense applications in combination with a suitable transfecting career [5]. We
have recently shown that xylonucleic acid (XNA), an artificial RNA analog, undergoes spontaneous
unzipping on the surface of both SWCNT [6] as well as graphene [7] under various physiologically
relevant simulation conditions. The extent of XNA unzipping assisted by either of the nanostructures is
much faster than a naturally occurring RNA with identical sequence of nucleobases. We propose that the
combination of XNA and a flat graphene sheet is best suited for therapeutics since graphene with a
lower surface curvature ensures the optimal unwinding in XNA which in turn, can provide a long term
protection against the expression of a fatal gene in human serum [7].
References:
1. Ghosh, S.; Patel, N.; Chakrabarti, R. J. Phys. Chem. B 2016, 120, 455 – 466.
2. Ghosh, S.; Dixit, H.; Chakrabarti, R. Chem. Phys. 2015, 459, 137­147.
3. Tereshko, V.; Minasov, G.; Egli, M. J. Am. Chem. Soc. 1999, 121, 470­471.
4. Ghosh, S.; Dixit, M. K.; Chakrabarti, R. Mol. Simul. 2016, 42, 715 – 724. 5. Zamecnik, P. C. and Stephenson, M. L. Proc. Natl. Acad. Sci. U. S. A. 1978, 4, 75, 280­281.
6. Ghosh, S.; Chakrabarti, R. J. Phys. Chem. B 2016, 120, 3642–3652.
7. Ghosh, S.; Chakrabarti, R. J. Phys. Chem. C 2016, 120, 22681 – 22693.
4
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5
First passage timescales of protein binding to target sites on DNA competing with nucleosomes
Dibyendu Das
Department of Physics, IIT Bombay, Mumbai, India
It is being increasingly realized that nucleosome organization on DNA crucially regulates DNA–protein
interactions and the resulting gene expression. While the spatial character of the nucleosome positioning
on DNA has been experimentally and theoretically studied extensively, the temporal character is poorly
understood. Many DNA binding proteins which regulate the activities of genes have to compete with
nucleosomes to access and bind to specific target patches on DNA. We analytically solve and also
numerically study this first passage problem of protein binding, within a kinetic model of binding­
dissociating nucleosomes. As a concrete application of our general result, we estimate timescales of
TBP binding to TATA sites, genome­wide in Saccharomyces cerevisiae. We find huge gene­to­gene
variability of the timescales. We further study the variation of TBP binding timescales for a specific
gene PHO5, as a function of factors which make its promoter switch from a transcriptional OFF to an
ON state. Reference:
1. Nucleic Acids Research, 44, 1630–1641 (2016)
6
Understanding 3­dimensional DNA organization in cells in the length­scale of a gene
P. Ranjith
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai – 400076, India
The fate of a cell is not just decided by the genetic code but also by the nature of the 3D organization of
the protein­ bound DNA, known as chromatin. Chromatin packaging is believed to be in a hierarchical
manner, and one of the crucial stages in the packaging is argued to be having a zig­zag structure with
specific width of 30 nm. However, most of the recent experiments failed to find any zig­zag­like ordered
arrangement of chromatin in living cells. In this work, we address this puzzle, and argue that any
regular, ordered, packaging of chromatin is unviable given that certain types of proteins can bind and
bend the chromosomal DNA.
7
Effect of confinement and stiffness on the conformational change of a semiflexible homopolymer
chain
Pramod Kumar Mishra
Department of Physics, Kumaon University, Nainital, India
We analyse the nature of the confinement of an infinitely long (and finite) linear semi­flexible homo­
polymer chain confined in between two geometrical constraints (A & B) under good solvent condition
in two dimensions. The constraints are stair shaped impenetrable lines. A lattice model of fully directed
self avoiding walk is used to list information of walks of the confined chain and the exact enumeration
technique is used for the canonical ensemble of conformations of the confined chain to discuss
equilibrium statistics of the chain. We obtain the probability of polymerization of the confined flexible
chain segments with either one end (polymer trains) or both the ends of the confined chain lying on the
stair shaped constraints (polymer bridge and arc). We have also calculated the force of confinement
exerted by the constraints on to the chain or the force exerted by the chain on the geometrical constraints
using grand canonical ensemble theory and discuss nature of variation of the force.
Keywords: Confined Polymer, Exact Results, Analytical Solution
8
dsDNA to ssDNA: A sliding platform for protiens
Garima Mishra
Department of Physics, Indian Institute of Technology, Kanpur, India
Seperation of double stranded DNA (dsDNA) into two single stranded DNA (ssDNA) is prerequisite for the
processes like replication and transcription. The inherent energetic heterogeneity involved in DNA makes the AT
rich region less stable than GC rich region and leads to the bubble formation localized in AT rich region. I will
discuss the role of the energetic hetrogeneity on the force­temperature diagram of DNA, which is studied
extensively from theoretical models for homogeneous DNA. The newly generated ssDNA from dsDNA is
thermodynamically less stable than dsDNA, and consequently, it spontaneously forms duplex secondary
structures (which inhibit subsequent DNA­processing reactions). A solution to this problem comes from
specialized ssDNA binding proteins (SSBs) that bind, protect, and stabilize the ssDNA structures. Complexes
between SSBs and ssDNA are often highly stable, but predicting their structures is challenging, mostly because of
the inherent flexibility of ssDNA and the geometric and energetic complexity of the interfaces that it forms. I will
discuss about my coarse­grained model that predicts the structure of SSB–ssDNA complexes and also sheds some
light over energetics and the underlying association mechanism.
9
Role of special crosslinks in structure formation of DNA polymer
Apratim Chatterji
Indian Institute for Science and Educational Research, Pune, India
Using data from contact maps of the DNA­polymer of E. Coli (at kilo base pair resolution) as an input
to our model, we introduce cross­links between monomers in a bead­spring model of a ring polymer at
very specific points along the chain. By suitable Monte Carlo Simulations we show that the presence of
these cross­links lead to a specific architecture and organization of the chain at large (micron) length
scales of the DNA. We also investigate the structure of a ring polymer with an equal number of cross­
links at random positions along the chain. We find that though the polymer does get organized at the
large length scales, the nature of organization is quite different from the organization observed with
cross links at specific biologically determined positions. We used the contact map of e­coli bacteria
which has around 4.6 million base pairs in a single chromosome. In our coarse grained flexible ring
polymer model we used 4600 monomer beads and observe that around 80 cross links are enough to
induce large scale organization of the molecule accounting for statistical fluctuations induced by thermal
energy.
10
Active Dynamics of Semiflexible Polymers
Abhijit Ghosh
Martin Fisher School of Physics, Brandeis University, USA
Active fluctuations, driven by processes that consume ATP, are prevalent in the living cells and are
mostly driven by different forms of molecular motors. Such motors often move and transmit forces
along biopolymers, which in general can be treated as semiflexible chains. We present a theoretical
analysis of the active (out of thermal equilibrium) fluctuation of semiflex­ ible polymers, using both
analytical and simulation methods. We find that enhanced diffusion, even superdiffusive, occurs in a
well­defined temporal regime, defined by the thermal modes of the chain and the typical timescale of
the activity. In addition, we find a dynamic resonance­like condition between the elastic modes of the
chain and the duration of the active force, which leads to enhanced spatial correlation of local
displacements. These results are in qualitative agreement with observations of cytoskeletal biopolymers,
and were recently observed for the dynamics of chromatin in interphase cells. We therefore propose that
the interplay between elasticity and activity is driving long­range correlations in our model system, and
may also be manifest inside living cells. Reference: 1. Dynamics of Active Semiflexible Polymers, Abhijit Ghosh and N S Gov, BioPhysical Journal,
107, 2014
11
Statistical Mechanics of Driven DNA: Theory and Simulations
Sanjay Kumar
Department of Physics, Banaras Hindu University, Varanasi ­ 221005, India
We propose a generic model of driven DNA under the influence of an oscillatory force of amplitude F
and frequency  and show the existence of a dynamical transition for a chain of finite length. We find
that the area of the hysteresis loop, A loop, scales with the same exponents as observed in a recent study
based on a much more detailed model. However, towards the true thermodynamic limit, the high­
frequency scaling regime extends to lower frequencies for larger chain length L and the system has only
one scaling Aloop ~ ­1 F2. Expansion of an analytical expression for Aloop obtained for the model system
in the low­force regime revealed that there is a new scaling exponent associated with force A loop ~ ­1
F2.5, which has been validated by high­precision numerical calculation. By a combination of analytical
and numerical arguments, we also deduce that for large but finite L, the exponents are robust and
independent of temperature and friction coefficient.
12
Probing DNA fluctuations, from the base pair to molecular conformations
Michel Peyrard
Laboratoire de Physique, Ecole Normale Supérieure de Lyon, France
The image of DNA as a static and rigid double helix does not match its biological activity. Actually
DNA is a highly dynamical entity. Its fluctuations allow the reading of the genetic code and its
flexibility is necessary to pack it in the nucleus of a cell or in a virus capsid.
We discuss different views of these fluctuations at various scales:
•
UV­laser two­photon ionization of the guanines, combined with standard biological methods can
probe the fluctuations at the scale of a few base pairs. We show that local fluctuations have
consequences that extend about 10 base pairs away.
•
An analysis of magnetic birefringence data, which probe the flexibility of DNA, points out the
role of base pair fluctuations on the flexibility of the molecule at large scale. •
Small angle X­ray and neutron scattering have been used to through a new light on the role of
some sequences to locate the nucleosomes at preferential positions, and on the recent debate on
the persistence length of short DNA chains.
References:
1. Santiago Cuesta­López, Hervé Menoni, Dimitar Angelov, and Michel Peyrard, Guanine radical
chemistry reveals the effect of thermal fluctuations in gene promoter regions, Nucleic Acids
Research 39, 5276­5283 (2011)
2. N. Theodorakopoulos and M. Peyrard, Base Pair Openings and Temperature Dependence of
DNA Flexibility, Phys. Rev. Lett 108 078104­1­4 (2012)
3. Adrián Gonázlez Rodríguez, Torben Schindler, Ramachandran Boopathi, Lionel Porcar, Andrew
Wildes, Nikos Theodorakopoulos, Santiago Cuesta­López, Dimitar Angelov, Tobias Unruh and
Michel Peyrard, Small Angle Scattering of the conformations and flexibility of a short DNA
sequence: the case of a Nucleosome Positioning Sequence, unpublished
13
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14
Thermal Denaturation of DNA
Y. Singh
Department of Physics, Banaras Hindu University, Varanasi ­ 221005, India
The thermal denaturation of DNA is believed to be first order phase transition. In the Poland­Scheraga
type models DNA is considered as being composed of a sequence of alternating bound segments and
denaturated loops(bubbles). The statistical weight (partition function) of a bubble is found to behave as
l­c. The nature of melting transition depends on value of exponent c. The talk will focus on finding value
of the exponent c.
15
Sequencing of semiflexible polymers through patterned pores
Rajneesh Kumar, Abhishek Chaudhuri, and Rajeev Kapri
Department of Physical Sciences, Indian Institute of Science Education and Research Mohali, Sector 81,
Knowledge City, S. A. S. Nagar, Manauli PO 140306, India
The knowledge of sequence of nucleotides within a DNA molecule is important for biological research
and various applications such as medical diagnosis, biotechnology, forensic investigations etc.
Experiments have shown that the passage of single stranded DNA and RNA molecules through
biological and synthetic nanopores result in a blockage of ionic current which would reflect the
incoming sequence of the DNA. Theoretical approaches to study polymer translocation through
nanopores have focused primarily on flexible polymers. We study the translocation of a semiflexible
polymer through pores with patterned stickiness. We show that the consequences of pore patterning on
the translocation time dynamics is dramatic and depends strongly on the stiffness of the polymer. We
utilize this dependence of translocation time on the microscopic structure of the pore and the polymer
rigidity, to use an effective sequencing strategy. This strategy which involves using multiple pores with
patterned surface energetics, can predict heteropolymer sequences with varying bending rigidity to a
high degree of accuracy.
16
Understanding diseaseome through molecular associations: A random matrix theory perspective
Sarika Jalan*
Centre for Biosciences and Bio­Medical Engineering, Indian Institute of Technology ,Indore ­ 452 020, India
Complex Systems Lab, Discipline of Physics, Indian Institute of Technology, Indore ­ 452 020, India
The inside of a cell is turbulent with activity, as enormous proteins, tiny molecules, and DNA strands wind
around each other to accompany thousands of interactions. The disease state is a consequence of various flaws in
molecular interactions that eventually result in the altered dynamics of the expressions of infected molecules. The
greatest challenge lies in understanding the relationship between these altered molecular interactions that leads in
the altered molecular pathways. Even after enormous researches, different diseases including cancers exhibit
extensive heterogeneity, which complicates the pathway procedures and cell functioning thus demanding new
tools to understand the cancer complexome at the basic molecular level. Further, the ample availability of various
types of experimental data from high­throughput techniques in molecular biology has lead to deeper insight of
various complex systems. Utilizing this vast information, rapid advancements in both experimental and
theoretical techniques have been performed in recent years. One such approach is the application of network
theory in combination with the spectral graph theory and Random matrix theory (RMT) approach on diseases
such as cancer. Cancer being a multifactorial complexome requires comprehensive understanding for its proper
diagnosis, screening and cure. Network science, spectral graph theory and RMT approach has shown its
tremendous success in a wide variety of disciplines, being it as diverse as the human brain, the world wide web,
scientific collaborations, communications and power systems engineering to molecular and population biology.
These tools uncover the complexity of the disease and understand disease at the fundamental level enabling us to
have a global view of the diseasome. Constructing the networks for different cancers provide a unique platform to
understand the altered interactions between the normal and the diseasedtissues, from the information and
literature available on various bioinformatics resources and helps improve our current knowledge of molecular
associations in diseases in a time efficient and cost effective manner. The technique may principally further lead
to improvements in prediction of new drug targets and insights not only into cancer biology but also other
diseases. This novel approach provides a clue to develop promising and nascent concept of single drug therapy
for multiple diseases as well as personalized medicine.
References:
1. Aparna Rai, Vipin Menon, and Sarika Jalan. "Randomness and preserved patterns in cancer network."
Scientific reports 4 (2014).
2. Sarika Jalan*, Alok Yadav. Assortative and disassortative mixing investigated using the spectra of graphs.
Phys. Rev. E 91, 012813 (2015).
3. Aparna Rai, Amit K. Pawar, and Sarika Jalan. "Prognostic interaction patterns in diabetes mellitus II: A
random­matrix­theory relation." Physical Review E 92.2 (2015): 022806.
4. Sarika Jalan, Krishna Kanhaiya, Aparna Rai, Obul Reddy Bandapalli, Alok Yadav. "Network Topologies
Decoding Cervical Cancer." PloS one 10.8 (2015).
5. Sanjiv K. Dwivedi, and Sarika Jalan. "Interplay of mutation and disassortativity." Physical Review E 92.2
(2015): 022802.
6. Alok Yadav, and Sarika Jalan. "Origin and implications of zero degeneracy in networks spectra." Chaos: An
Interdisciplinary Journal of Nonlinear Science 25.4 (2015): 043110.
7. Pramod Shinde, Alok Yadav, Aparna Rai, and Sarika Jalan. "Dissortativity and duplications in oral cancer."
The European Physical Journal B, 88, no. 8 (2015): 1­7.
8. Aparna Rai, Priodyuti Pradhan, Jyothi Nagraj, K. Lohitesh, Rajdeep Chowdhury, Sarika Jalan. “Understanding
cancer complexome using networks, spectral graph theory and multilayer framework.” Scientific reports (2017)
(in press)
Email: [email protected] 17
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18
The bubble­bound state of a triple­stranded DNA
Jaya Maji
Department of Physics, Indian Institute of Science and Educational Research, Bhopal, India
The presence of a thermodynamic phase of a three­stranded DNA, namely a phase of bubbles of two
bound and one single strands, is established by using exact real space renormalization group (RG)
transformations for dimensions d>2 and equivalent exact computations for fractal Sierpinski gasket of
dimension d<2. In contrast to the Efimov­DNA, where three strands are bound without duplex binding,
a new phase of DNA with pairwise binding but without three chain contacts appears on the bound side
of the two chain phase boundary. The strand exchange between one strand of the pair and the single
strand keeps the phase stable. This new phase, which is characterized by a separate RG flow in d>2, can
be identified from direct calculations for d<2.
19
Nano­Technologies for Single Nucleotide Polymorphisms (SNP) Detection
Ajay Agarwal
CSIR­Central Electronics Engineering Research Institute & Academy of Scientific & Innovative Research, PILANI (RAJ.) – 333 031, INDIA (E­mail: [email protected])
Nanotechnologies along with standard silicon micro­fabrication technologies have enabled novel nano­
dimensional materials, structures and eventually devices which find numerous applications in the field
of medical diagnostics, drug delivery, electronics, energy production, detecting food adulterants, water
pollutants, etc. With the increasing awareness, healthcare is particularly in focus that includes early
diagnosis, drugs discovery, point­of­care solutions, etc. For these bio­medical applications, specific and
sensitive detection of various biological and chemical species becomes crucial.
Single nucleotide polymorphism (SNP) detection technologies are important to know new
polymorphisms and to determine the allele(s) of a known polymorphism in target sequences. SNP
detection technologies have been labor intensive, time consuming and expensive since recently where
some automated, efficient, and relatively inexpensive methods have been demonstrated. The number of
SNP genotyping methods increasing but the demand for SNP detection is enormous. A new approach to
detect SNPs in multiplexed scenario is presented using nano­structured biosensors.
References:
1.
2.
3.
4.
5.
6.
7.
8.
Ajay Agarwal, et al., Sensors and Actuators A: Physical, 145­146, 207 (2008)
N. Singh, A. Agarwal, et al., IEEE Transactions on Electron Devices, 55, 3107 (2008)
Z. Gao, A. Agarwal, et al., Analytical Chemistry, 79 (9), 3291 (2007)
X. Bi, A. Agarwal, et al., Biosensors Bio­electronics, 23, 1442 (2008)
T­S Pui, Ajay Agarwal, F. Ye, N. Balasubramanian, P. Chen, Small, 5, 208 (2009)
R Prajesh and Ajay Agarwal, BioNanoSci, 2, 218 (2012)
R Prajesh, P B Agarwal and Ajay Agarwal, BioNanoSci, 2, 223 (2012)
Ranjan K Maurya and Ajay Agarwal, Fluid­FET Controller for Microfluidic Devices, IEEE Sensors, doi­
10.1109/JSEN.2015.2456233.
20
Spontaneous formation of membrane tubes
Anirban Sain, Indian Institue of Technology, Bombay, Mumbai
Membrane tubes are common in Biology at the level of single cells. Many recent examples have
emerged where tubes grow from phospholipid vesicles due to ATP dependent active forces. We will
discuss one such case where tubes seem to spontaneously grow from polymer coated vesicles.
21
Rupture dynamics in model polymer systems
Rupam Borah and Pallavi Debnath
*
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee­247667, India (E­mail: [email protected] )
I will discuss the rupture dynamics of a model polymer system to capture the microscopic mechanism
during relative motion of surfaces at the single polymer level. Our model is similar to the model for
friction introduced by Filippov, Klafter, and Urbakh [Filippov et al., Phys. Rev. Lett., 2004, 92,
135503]; but with an important generalization to a flexible transducer (modelled as a bead spring
polymer) which is attached to a fixed rigid planar substrate by interconnecting bonds (modelled as
harmonic springs), and pulled by a constant force FT. Bonds are allowed to rupture stochastically. The
model is simulated, and the results for a certain set of parameters exhibit a sequential rupture
mechanism resulting in rupture fronts. A mean field formalism is developed to study these rupture fronts
and the possible propagating solutions for the coupled bead and bond dynamics, where the coupling
excludes an exact analytical treatment. Numerical solutions to mean field equations are obtained by
standard numerical techniques, and they agree well with the simulation results which show sequential
rupture. Within a travelling wave formalism based on the Tanh method, we show that the velocity of the
rupture front can be obtained in closed form. The derived expression for the rupture front velocity gives
good agreement with the stochastic and mean field results, when the rupture is sequential, while
propagating solutions for bead and bond dynamics are shown to agree under certain conditions.
References:
1. R. Borah and P. Debnath, Soft Matter, 2016, 12, 4406 – 4417.
22
Monte Carlo study of periodically driven DNA
M. Suman Kalyan* and Rajeev Kapri$
Department of Physical Sciences, Indian Institute of Science Education and Research Mohali, Sector 81,
Knowledge City, S. A. S. Nagar, Manauli PO 140306, India
Email: *
[email protected], [email protected] We study the hysteresis in unzipping of a double strand DNA (dsDNA) subjected to a periodic force,
with amplitude g0 and frequency , using Monte Carlo simulations. In an earlier study [1] it was found
that at a fixed temperature the loop area A loop increases as  is increased. It reaches a maximum at
frequency , which depends on force amplitude g0, and then decreases. It was found that Aloop decreases
monotonically for lower values of g0 but shows an oscillatory behavior for higher values of g0 . Here, we
study the temperature dependence of the hysteresis loop as a function of temperature T, amplitude g 0,
and frequency . We find that as temperature is increased A loop starts showing oscillatory behavior even
for lower values of g0 . We also study the scaling behavior of Aloop as a function of T, g0 , and .
References:
1. R. Kapri, Phys. Rev. E, 90, 062719 (2014).
23
Understanding DNA Based Nanostructures using Molecular Simulations
Himanshu Joshi and Prabal K. Maiti
Centre for Condensed Matter Theory, Department of Physics, Indian Institute of Science, Bangalore 560 012, India
DNA is arguably the most important biological molecule. Recent decades have witnessed the synthesis
of many DNA nanostructures with proposed applications in nanotechnology. State of the art molecular
dynamics (MD) simulations can be very useful to understand the microscopic structure of these self­
assembled structures at nanoscale. We have developed algorithms to build very accurate 3­d atomistic
models of various DNA nanostructures like crossover DNA molecules, DNA nanotubes (DNTs) and
DNA polyhedra. We investigate the structure, stability and mechanical properties of various DNA
nanostructures in salt solution. We find that the persistence length of DNA nanotubes is of the order of
micrometer. We have also examined the interaction of DNA nanotubes embedded in the lipid bilayer
membranes. We discover that the local rearrangement of lipid molecules can stabilize the DNA
nanotubes in the bilayer and DNA backbone modification is not necessary for the partitioning of DNTs
in lipid bilayer. The Ohmic conductance measured from I­V characteristics of the ions channel varies
from 4.3 to 20.6 nS with ionic strength. The simulation studies with atomistic model of DNA
icosahedron reveal the dynamical behavior of the structure and its interaction with encapsulated cargo.
We believe that our simulation studies will give further impetus in the design and development of
structural DNA nanotechnology.
References:
1. Joshi et al. PCCP 2015, 17, 1424­1434.
2. Joshi et al. ACS Nano 2016, 10, 7780­7791.
3. Bhatia and Joshi et al. Nature nanotechnology 2016.
24
DNA in a crowding environment
Anurag Singh, Suparna Khatun and Amar Nath Gupta
Biophysics and Soft Matter Laboratory, Department of Physics, IIT Kharagpur, India­721302
With a view to understand compaction of DNA in crowded conditions, we have measured the radius of
gyration of plasmid in its supercoiled and linear forms in the presence of dextran nanoparticles through
light scattering. It was observed that the supercoil initially expands and subsequently compacts with
increasing volume fraction of the dextran having smaller size. The plasmid does not collapse into a
condensed state. Our results show first, the supercoil expands through a modification of its geometrical
properties by the depletion induced attraction between the two opposing duplexes of the superhelix and
second, the molecule gets compressed due to the depletion of nanoparticles in the interior of the coil
with concomitant imbalance in osmotic pressure between the coil and surrounding medium. The
antagonistic nature of these two aspects of crowding results has a much more pronounced and richer
effect on the dimensions of supercoiled plasmid than the effect of variation in ionic strength. We have
also studied the effect of binding ligand to DNA which changes the elastic property of DNA at single­
molecule level through AFM. When a ds­DNA molecule is overstretched in the presence of ligands, it
undergoes a co­operative structural transition based on the externally applied force, the binding constant
of the ligands to the DNA, the concentration of the ligands and the ionic strength of the supporting
medium. These transitions were studied by the extended and twistable worm­like chain model. We
conclude that besides ionic strength, interacting proteins and content of AT and GC base pairs, the
ligand binding or intercalation with the ligands is an important parameter which changes the stiffness of
DNA.
25
Role of Bio­sensors in Defense
Alok Shah
Life Sciences Research Board (LSRB), DRDO HQ., New Delhi­110011
Defense is one of the largest consumers of fresh, semi­processed and processed food and other
agricultural commodities. In a country like India, the lack of phyto­ and phyto­sanitary protocols in the
agri­food market has potentially increased biological, chemical and physical threats to food products,
catapulting a demand both in Defense and the civil market at large on more effective and better process
control, quality and safety of these products. Biosensors can play a pivotal role in controlling production
processes and ensuring greater agricultural and food quality by putting in place fast, reliable and
affordable monitoring procedures. The advantage of bio­sensors lie in providing an alternate mechanism
to conventional analytical tools and techniques in terms of size, cost­effectiveness, specificity, rapid
response, sensitivity, repeatability and precision. Food and agricultural production chain is vulnerable to
different kind of threats at every step in terms of loss of quality and susceptibility to transmit diseases
through falling prey to microbial, fungicidal, pesticidal, weedicidal and insecticidal invasions. These
microbial, biological, chemical and/or physical threats can be due to environmental contamination or
failures to stick to standard food handling, processing, packaging and distribution quality procedures
and protocols. A properly developed biochip in a biosensor can capture the molecular and genetic
signatures of various contaminants. Biosensors can not only detect, analyse and quantify molecules of
different biological origins but also throw light on the quality of food or agricultural produce in terms of
their residual loads of esticides, fertilizers, agro­chemicals, dioxins; besides, biosensors can provide
information on contaminated water, soil residues, genetically modified organisms, pathogenic
microflora and their toxins, food anti­nutrients, allergens, drug residues, additives and hydrocarbons,
etc. Biosensors can also diagnose changes in the food composition in the aftermath of post­harvest
practices, operations and processing through real­time monitoring of various variables such as pH,
temperature, pressure, oxygen, flow and volatile components; and, thus, help in the implementation of
hazard analysis and critical control points (HACCP) by identification and detection of food borne
pathogenic threats, chemical and bio­chemical contaminants. The need of the hour is to develop a multi­
utility bio­sensor that embeds, within its design, features to function as a chemical, temperature,
pressure and pH­sensor as well, in addition to picking up molecular and genetic traits of more than one
microorganism or an analyte. An intelligently designed and developed biosensor can effectively screen
air, water, soil, agro­material, food, water bodies, fresh and waste plant and animal material to mitigate
the bio­threat paradigm by rapid detection of biothreat pathogens and agents and their toxic, and or
pathogenic analytes and metabolites. 'Detect to Protect' biosensors, at different scales of development
and eco­deployment, can provide an effective shield against biological warfare (BW) agents.
Email: [email protected]
26
27
A transcriptomic analysis pipeline decoding network of genes involved in different stages leading
to acquisition of cancer drug resistance
J Nagraj, M. Vasudevan, S. Jadav, G. Mishra, S. Mukherjee, S. Chowdhury S and Rajdeep Chowdhury
Department of Biological sciences, BITS, Pilani, Rajasthan 333031, India
Existing evidences suggest survival of a distinct population of cancer cells that resist chemo­therapeutic
shock, eventually evolving into drug resistant cells. This is considered, a cause to treatment failure and
subsequent relapse. Identifying appropriate drug/s that can eliminate these drug­tolerant “persisters” still
remains an issue in cancer therapy. Hence, deeper understanding of the distinctive genetic signatures
and genetic boundaries between untreated cells, drug treated cells, persisters following drug shock and
persister­derived resistant cells is of utmost importance. In this study, through deep sequencing of both
mRNA and small RNAs we have generated a transcriptomic network that provides critical insights into
the molecular events leading to emergence of persister sub­population of cells post cisplatin shock, and
strategies acquired by these cells to evade persister bottleneck leading to emergence of drug­resistant
cancer cells. The conventional drug, cisplatin which is an integral part of current treatment regime for
multiple cancer types is opted for this study. Both receptor mediated signaling and intracellular
signaling were found to be de­regulated. A core network of genes showing altered expression were
identified across the different stages of acquisition to resistance. This study is uniquely designed to
better understand the series of genetic events leading to the surfacing of drug resistance in osteosarcoma
cells, and implications from this study can have potential future therapeutic impact.
28
ICRF­193 delays spindle elongation and produce archery bow phenotype in dividing fission yeast
cells
Rajesh Mehrotra1,#, Norihiko Nakazawa1, and Mitsuhiro Yanagida1,*
1
G0 Cell Unit, Okinawa Institute of Science and Technology Promotion Corporation, Uruma, Okinawa 904­2234, Japan
# Department of Biological sciences, BITS, Pilani, Rajasthan 333031, India
ICRF­193, a noncleavable, complex stabilizing topoisomerase (topo) Ⅱ　inhibitor,　has been shown to
target topo Ⅱ in mammalian cells. With the aim of elucidating the roles of topo Ⅱ in dividing S. pombe
cells, we examined the effects of ICRF­193 treatment on such cells. ICRF­193 treated cells shows
chromosome segregation defect and archery bow phenotype. This phenotype is different than top2­191
mutant cells phenotype. The study involving cs nda3 indicated that ICRF­193 treatment delays
metaphase to anaphase transition in S. pombe cells compared to the DMSO treated control cells. It is
reported that anaphase inhibitor securin is kept stable during such delay. The spindle characteristics
were severely affected by the drug treatment. Phase2 and Phase3 of spindle elongation were not distinct
as previously reported for top2­191 mutant cells but more interestingly, the ICRF­193 treated cells
showed constant spindle elongation speed in Phase2 and Phase3 supporting the delay induced by ICRF­
193 treatment which ultimately results into archery bow phenotype.64 percent of the dividing cell
showed archery bow phenotype after 2 hours of ICRF­193 treatment. Using fixed cells of Top2­GFP, we could observe the dot signal of GFP in ICRF­193 treated cells
compared to the DMSO treated cells, indicating the trapped topo Ⅱ on the DNA after ICRF­193
treatment. In short ICRF­193 treatment is effective in S. pombe cells. ICRF­193 affects the dividing S.
pombe cells by inhibiting the spindle characteristics and results in archery bow phenotype. This is the
first report of ICRF­193 treatment in S. Pombe. The data will be presented in the conference.
29
Elastic properties and conformational changes of DNA: An all­atomistic molecular dynamics study
Ashok Garai
Department of Physics, The LNMIIT, Jaipur, India
Active Biological processes, like transcription, replication, recombination, DNA repair, and DNA
packaging encounter bent DNA. Machineries associated with these processes interact with the DNA at
such a short length scale. Thus the study of elasticity and conformational changes of DNA at such length
scale is crucial. Molecular dynamics simulations can be used to extract various conformational during
stretching and other biomolecular properties of DNA through a systematic study of fluctuations at the
atomic level. Atomistic molecular dynamics simulations aid to calculate different elastic properties of
various DNAs starting from short free DNA to nucleosomal DNA. Furthermore, it is found that
macroscopic elastic theory is not adequate to calculate the elastic properties of various short DNAs.
Stretching of DNA under different pulling protocols can provide a detailed picture of various
conformational changes of DNA and also brings forth fundamental molecular understanding of DNA
stretching mechanism. Such realistic studies will certainly enrich the pool of techniques to interpret the
experimental data as well as motivate to perform new experiments.
30
Poster Presentations
31
Change in flexibility of DNA with binding ligands
Anurag Singh and Amar Nath Gupta1
Soft Matter Laboratory, Department of Physics, Indian Institute of Technology Kharagpur, India­721302
The percentage and sequence of AT and GC base pairs and charges on the DNA backbone contribute
significantly to the stiffness of DNA. This elastic property of DNA also changes with small interacting
ligands. The single­molecule force spectroscopy technique shows different interaction modes by
measuring the mechanical properties of DNA bound with small ligands. When a ds­DNA molecule is
overstretched in the presence of ligands, it undergoes a co­operative structural transition based on the
externally applied force, the mode of binding of the ligands, the binding constant of the ligands to the
DNA, the concentration of the ligands and the ionic strength of the supporting medium. This leads to the
changes in the regions­ upto 60 pN, cooperative structural transition region and the overstretched region,
compared to that of the FEC in the absence of any binding ligand. The cooperative structural transitions
were studied by the extended and twistable worm­like chain model. Here we have depicted these
changes in persistence length and the elastic modulus constant as a function of binding constant and the
concentration of the bound ligands, which vary with time. Therefore, besides ionic strength, interacting
proteins and content of AT and GC base pairs, the ligand binding or intercalation with the ligands is an
important parameter which changes the stiffness of DNA.
1
[email protected] , [email protected]
32
Study of translocation of ssDNA and dsDNA through nanopore sites
Anurag Upadhyay, Dibyajyoti Mohanta, S. Kumar* and D. Giri
Department of Physics, IIT BHU, Varanasi ­ 221005, India *
Department of Physics, Banaras Hindu University, Varanasi ­ 221005, India
(1 & 2 are presenting co­authors)
We examine double­stranded and single­stranded DNA translocation through nanopores by means of
molecular dynamics (AMBER and NAMD software) and also Monte carlo simulation.The DNA motion
is found to be independent of the cross­section of nanopores.This happens due to the competition
between two forces­ the adhesion of DNA bases to the nanopore sites and the mechanical forces which
act along the length of the DNA as it is attached to one end. We also try to understand the Efimov effect
of triple stranded DNA.
Denaturation of DNA at high salt concentrations
Arghya Maity and Navin Singh
Department of Physics, Birla Institute of Technology & Science, Pilani
(Email: [email protected])
Intracellular sodium triggers a cell to progress in to cell division. So, intensifying of Nacl makes a
dreadful manifestation of cell. The DNA phase transition effect has been studied and established at low
strength of salt in theoretical and experimental aspects. Intracellular positive ions widen nucleic acid
flexibility through nullifying the negative charges on the phosphates of DNA strand. So dsDNA chain
gets more stability. However the behaviour of DNA at high salt strength is still theoretically ambiguous
beacause the experimental studies of salt on DNA apprise a hostile nature after a certain strength. How
the DNA strand breaks in this hypotonic medium so promptly and turn out to be unstable, is the aim of
our manuscript. We outline a corelated biological phenomenon like tumor cells specifically Cancer cells
since these type of cells carry a dissimilar aspect from normal somatic cells of high intracellular
concentration of Nacl. We try to delineate this nature of salt in theoretical aspect using Peyrard Bishop
Dauxois model and also try to scrutinize the stability and unstability slope of this nature of salt from the
graph.
33
Understanding Protein­Protein Interactions of Cancer Complexome
Aparna Rai1,a, Priodyuti Pradhan2, Jyothi Nagraj3, K. Lohitesh3, Rajdeep Chowdhury3, and Sarika Jalan1,2,b
1
Centre for Biosciences and Bio­Medical Engineering, Indian Institute of Technology, Indore ­ 453552, India
2
Complex Systems Lab, Discipline of Physics, Indian Institute of Technology, Indore ­ 453552, India
3
Department of Biological Sciences, Birla Institute of Technology & Science, Vidya Vihar, Pilani, Rajasthan, 333031, India
Email: [email protected], [email protected] , Group page: http://iiti.ac.in/people/~sarika/ Different diseases including cancers exhibit extensive heterogeneity, which complicates the pathway
procedures and cell functioning. Development of statistical tools inspired from other branches of
sciences, particularly from graph theory and random matrix theory enables us to have a global view of
the diseasome. Constructing the networks for different types of cancers provide a unique platform to
understand the altered interactions in the diseased tissues, utilizing the information and literature
available on various bioinformatics resources. Cancer being a multifactorial complexome requires
comprehensive understanding for its proper diagnosis, screening and cure. These tools uncover the
complexity of the disease and understand disease at the fundamental level. Hence, exploring molecule­
molecule associations through the holistic combined framework of the systems biology approach,
network theory and multilayer approach is expected to trace differences in the associations of normal
and disease states and improve our current knowledge of molecular associations in diseases in a time
efficient and cost effective manner. It may principally be lead to further much required improvements in
prediction of new drug targets and in sights into the cancer biology.
References:
1. Aparna Rai, Priodyuti Pradhan, Jyothi Nagraj, K. Lohitesh, Rajdeep Chowdhury, Sarika Jalan,
“Understanding cancer complexome using networks, spectral graph theory and multilayer
framework.” Scientific reports (2017) (in press).
Study of Lennard­Jones systems using Molecular Dynamics Simulation
Pallabi Kundu and Pankaj Mishra
Department of Applied Physics, Indian Institute of Technology (Indian School of Mines) Dhanbad­826004, India
Email: p
[email protected]
We discuss the numerical simulation techniques as a method of scientific study of real systems. Various
simulation techniques has been described with special emphasis on molecular dynamics simulation
which was studied in details and discussed followed by a few illustrative examples. A system of
particles interacting via Lennard­Jones potential is studied and a few static properties are calculated.
Computation was done in the regime of MD simulation following the constant energy criteria where the
kinetic energy of the system is a function of temperature alone.
34
AC Magnetic Fields Dependent Measurement on DNA Engineered Cobalt Ferrite For Biomedical
Application
Arpita Das1, Debarati De1, Prof. Ajay Ghosh1, Madhuri Mandal2
1
CRNN, University of Calcutta,Kolkata, 700098, India
2
S.N.Bose National Centre for Basic Science, Kolkata 700098, India
E­Mail address (corresponding author): [email protected]
The cobalt ferrite nanoparticles have suitable property which may provide a new direction in medical
science.These particles can be controlled by the magnetic fields from outside the body.
For biomedical application these cobalt ferrite nanoparticles was properly engineered with DNA.Here
cobalt ferrite nanoparticles were synthesized on DNA scaffold by wet chemical co­precipitation method.
Different batches of particle were synthesized by varying the amount of DNA.The cobalt ferrite
nanoparticles attached with DNA was analyzed by infrared spectroscopy (IR), scanning electron
microscope (SEM), Transmission electron microscope(TEM), squid, X­ray diffraction (XRD), Dynamic
light scattering (DLS) etc. From XRD data it was confirmed that the above mentioned nanoparticles is
cobalt ferrite in pure phase and from IR and SEM analysis it was shown that cobalt ferrite nanoparticles
were attached with DNA. It was investigated from SQUID data that with increasing amount of DNA,
cobalt ferrite nanoparticles showed different magnetic properties. From DLS data the exact size of the
particle was concluded. From IV­CV measurement it shown the Negetive Differential Resistance which
will be helpful for charge storage for future application. The DNA bounded cobalt ferrite also tagged
with fluorescence dye so that the path of their movement can be tracked from outside of the body.
A comparative study have been done by keeping the different batches of MNP (magnetic nano particle)
attached in cancer cells in the Hyperthermia circuit for varying time. This particle under AC magnetic
field produce suitable heat which is very significant for Hyperthermia Therapy. Fig. 2: Bio­SEM image of DNA attached MNP
Fig. 1: Circuit for Hyperthermia Treatment
References
1. Johannsen, M., et al, Hyperthermia, 21, 635(2005)
2. Ferrari, M., Nat. Rev. Cancer 5, 161, (2005)
35
DNA functionalized cobalt ferrite nanoparticles: a betterment in internalization with cell and
cytotoxicity level
Debarati De1, Arpita Das1, Prof. Ajay Ghosh1, Madhuri Mandal2 1
CRNN, University of Calcutta, Kolkata, 700098, India
2
S.N.Bose National centre for Basic Science, Kolkata 700098, India
E­Mail address (corresponding author): [email protected]
Different batches of cobalt ferrite nanoparticles (CoFe2O4, CoFe2O4­DNA) with average size in the
range between 20 nm were synthesized using the Wet chemical co precipitation method. The cobalt
ferrite nanoparticles attached with DNA was analysed by infrared spectroscopy (IR), X­ ray diffraction
(XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), squid etc.
Cytotoxicity and biocompatibility of these particles were also analyzed in human mammary carcinoma
cell lines (MDAMB­231) where different amount of doses of different batches were added to the cells.
Here Cell viability is measured as the percent live cells compared with untreated control. From the study
it was seen that the CoFe 2O4 NPs shows itself cytotoxic effect in case of cancer cell but is biocompatible
in case of normal peripheral blood mononuclear cell (PBMC). From the above mention study it was also
seen that the DNA bound cobalt ferrite (CoFe2O4­DNA) NPs shows less toxic effect and better
internalization of particles compared to the bare cobalt ferrite (CoFe2O4) Nps.
Fig 1: Without DNA + RITC
Fig 2: 0.4 DNA NPs + RITC
Fig 3: 0.8 DNA + RITC
Figure: Internalization of cobalt ferrite NPs and different amount of DNA bound cobaltferrite NPs in MDAMB­
231 cell.
36
Role of DNA bending non­histone proteins in higher­order structure of Chromatin
Gaurav Bajpai1, Ishutesh Jain1, Mandar M. Inamdar2, Dibyendu Das3, Ranjith Padinhateeri1
1
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India
2
Department of Civil Engineering, Indian Institute of Technology Bombay, Mumbai, India
3
Department of Physics, Indian Institute of Technology Bombay, Mumbai, India
In eukaryotes, DNA is packaged inside the nucleus in the form of chromatin. Chromatin is a
combination of protein and DNA. We know from our molecular biology text books that three levels of
chromatin organization are found in the cell. (i) DNA wraps around histone proteins form nucleosome,
the beads on a string structure. (ii) Multiple nucleosomes wrap into a 30 nm fiber consisting of
nucleosome arrays in their most compact form. (iii) Higher­level DNA packaging of the 30 nm fiber
into the metaphase chromosome. In lots of experiments it has been found that 30 nm structure exists in
vitro. But in vivo evidence of this type of structure is not very visible. Why we sometimes see 30 nm
structure and sometime not, is a puzzle. The fundamental physical principles behind the formation of a
regular 30­nm structure are the orientations of DNA entering/exiting nucleosomes and the bending
elasticity of linker DNA between nucleosomes. In the conference, we present our theoretical model
which explain that once we consider the presence non­histone protein (nhp6, HMG etc.) that bind and
locally bend linker DNA, the existence of regular structure are not feasible. Our model is comparable
with recent Micro­C experiment which explain chromatin structures inside the cell are irregular and
contact probability of neighbor nucleosomes and next neighbor nucleosomes are equal.
References:
1. Bajpai G, Jain I, Inamdar MM, Das D, Padinhateeri R, Binding of DNA­bending non­histone proteins destabilizes regular 30­nm chromatin structure, PLoS Comput Biol 13(1): e1005365 (doi:10.1371/journal.pcbi.1005365)(2017)
Kinetics of Tumbling of polymers in shear flow
Sadhana Singh and Sanjay Kumar
Department of Physics, Institute of Science, Banaras Hindu University, Varanasi, 221005 India
To study the kinetics of tumbling and conformational change of polymer system in shear flow, we have
developed a coarse­grained model for flexible polymer chain. Based on the numerical simulation, the
static and dynamic properties of a single polymer in shear flow is studied. The observed properties are in
general agreement with results reported in the literature. The cyclic motion phenomenon is studied by
power spectrum density analysis.
37
Codon based co­occurrence network motifs in human mitochondria
Pramod Shinde*, Camellia Sarkar, Sudeep Tiwari$, Sarika Jalan
Complex Systems Lab, Discipline of Physics, Indian Institute of Technology, Indore­ 453552, India
Email: *[email protected], [email protected] (presenting co­authors)
The nucleotide polymorphism in human mitochondrial genome (mtDNA) tolled by codon position bias
plays an indispensable role in human population dispersion and expansion. By analysing codon position
bias captured by nucleotide co­occurrence over mtDNA, we develop a powerful network model to
describe complex mitochondrial evolutionary patterns between codon and non­codon positions. It is
interesting to report a different evolution of Asian genomes than those of the rest which is divulged by
network motifs in non­coding regions. Most notably, codon motifs apparently underpin the preferences
among codon positions for co­evolution which is probably highly biased during the origin of the genetic
code accompanied by their comparison with random variants. Our analyses manifest that codon position
co­evolution is very well conserved across human subpopulations as well as independently maintained
within human sub­populations implying the selective role of evolutionary processes on codon position
co­evolution. Ergo, this study provides a framework to investigate cooperative genomic interactions
which are critical in underlying complex mitochondrial evolution.
Statistical mechanics of a polymer chain attached to the interface of a cone­shaped channel
Sanjiv Kumar, S. Kumar and D. Giri#
Department of Physics, Banaras Hindu University, Varanasi ­ 221005, India
#
Department of Physics, IIT­BHU, Varanasi ­ 221005, India
We study equilibrium properties of a short polymer chain attached to the one end of a cone­shaped
channel. Depending on the solvent quality (good or poor) across the channel, a polymer chain can be
either inside or outside the channel or both. Exact results based on a short chain revealed that when the
solvent quality remains the same across the interface, the polymer prefers to stay outside the channel.
Surprisingly, when the quality of solvent inside the channel is relatively poor than the outside, even
then, polymer prefers to stay outside at lower temperature. Our results demonstrate that a slight variation
in the solvent quality can drag polymer chain inside the pore and vice versa. Furthermore, we also report
the absence of crystalline (highly dense) state when the pore­size is less than the certain value. We
delineate the possible mechanism, which may have potential application in understanding of the
biological processes.
38
Translocation of a semiflexible polymer through sticky pores
Rajneesh Kumar*, Abhishek Chaudhuri and Rajeev Kapri$
Department of Physical Sciences, Indian Institute of Science Education and Research Mohali, Sector 81,
Knowledge City, S. A. S. Nagar, Manauli PO 140306, India
Email: *[email protected], [email protected]
We study the driven translocation of a homogeneous semiflexible polymer through an extended pore
that interacts with the polymer. We consider pores with different patterned stickness and study how the
translocation process depends on the bending stiffness of the polymer. We find, similar to earlier
studies, that a stiffer polymer takes more time to translocate through patterned pores. We then consider
the driven translocation of a semiflexible chain consisting of alternate blocks of stiff and flexible
segments through the patterned pores. In this case we find that the translocation time depends strongly
on the pore pattering. The waiting time distributions, of the monomers of the polymer, which gives
extensive information of the translocation dynamics, show novel features attributed to the friction
experienced inside the pore due to varying pore­polymer interactions and finite lengths of the pores.
Melting and Unzipping of Three­Stranded DNA
Tanmoy Pal and Sanjay Kumar
Institute of Science, Department of Physics, Banaras Hindu University, Varanasi ­ 221005, India.
We study thermal melting and forced unzipping of a short three­stranded DNA comprised of two
identical single strands made of T bases only and a third strand of equal length but made of A bases
only. By allowing the Watson­Crick base pairing, implemented through Lennard­Jones potential, we do
Langevin dynamics simulation for a range of temperature and unzipping force. At zero unzipping force,
be low a critical temperature, the system stays in a three­stranded bound state which has been reported
in the literature as ”mixed state”. Next, we apply an unzipping force at the ends of the two T­strands and
study the end­point separations as a function of the unzipping force. As direct Hydrogen bonding
between two T­strands is not allowed, we get interesting force­extension curves which we can explain
through quantities related to denaturation bubbles.
39
40
41
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