Abstract |
Electronics has come a long way. From imposing mainframes to slick
handhelds, we have seen it all. The computing technologies are
decreasing in size - in the early days a computer filled a room; now
the computing power that can fit in our pockets vastly exceeds the
fastest mainframes available just a few decades ago. It's time to
imagine how we might build computing technologies at the
nanoscale. Such technologies might enable us to monitor environments
at a scale not possible today, or could even diagnose diseases in
tissue samples. With the ever decreasing size and increasing
computational accuracy, the challenges in better designs are
enormous. DNA nanotechnology holds a promising future in this
area. Realisation of logic gates from DNA molecules and development of
DNA nanomachines is a clear indication that DNA could replace the
complex electronic circuits that are used in customer goods ranging
from washing machines to mobile devices.
What is DNA? DNA (DeoxyriboNucleic Acid) is the heredity material
found in all living organisms by virtue of which they inherit several
characteristics from their biological parents. These DNA molecules
have specific segments called genes that act as a store house of
information. Each DNA molecule consists of two strands that are long
chains (polymers) of small nucleotide units. These are attached
together by bases, namely Adenine (A), Cytosine (C), Guanine (G) and
Thymine (T), occurring at regular intervals. The whole structure can
be imagined as a twisted ladder (double helix).
Recently, DNA has found several innovative uses that go beyond
genetics and healthcare. Outside of the cell, we can design DNA
molecules to fold into more interesting structures, using the
base-pairing principle -- A forms a base pair with T and G forms a
base pair with C. Not only the final structures, but the "pathway" --
the series of intermediate structures formed by molecule before it
reaches a stable structure -- is also of interest because it provides
a means to design molecules with moving parts that have useful
mechanical properties or can navigate a surface. In 2004, Rothemund et
al. proved DNA to be "capable of implementing any desired algorithm
for computation or construction tasks." DNA nanotechnology can now be
used to construct many interesting structures, motors or circuits that
have the potential to provide a paradigm shift from the current
integrated circuit technology where all the circuits are
hardwired. Many complex structures like a nanoscale octahedron have
been obtained from DNA by virtue of molecular self-assembly -- the
process by which molecules adopt a defined arrangement without
guidance or management from an outside source. In 2010, scientists
from several universities developed nanoscale DNA robots widely known
as DNA walkers.
Early designs like "DNA tweezers" used a few DNA strands. Several
recent structures use a few hundred strands. Clearly, we will be
looking for structures comprising thousands and soon millions of DNA
strands. There are several challenges that we face when scaling up the
process of generating the requisite DNA molecules. These challenges
can mainly be attributed to the unpredictability of folding pathways
for multi-stranded structures. Since DNA is used as a structural
material in these cases rather than as genetic material, it is
important to develop a clear understanding of the reaction dynamics
and structural details. Here, specific interactions between two or
more DNA molecules have to be taken into account to determine the
structures formed by molecular recognition.
One part of the project that I'm involved in at the BETA
(Bioinformatics, Empirical and Theoretic Algorithms) lab concentrates
on multi-stranded structures described above. For a single strand,
structure prediction is quite simple. But for the increasing
combinatorial possibilities of multi-stranded structures, the problem
becomes very complex. We are advancing understanding about the
computational difficulty of predicting multi-stranded structures,
based on the principle of free energy minimization. The other part of
the project involves the kinetics and reaction details of DNA strand
displacement. Many enzyme-free constructions are now available like
the hybridisation chain reaction. We concentrate on a fast and
reversible method for strand displacement reactions called the toehold
exchange process. It is not clearly understood whether occurrences of
identical sequences confuse the folding pathways or actually assist in
bond formation. We run simulations that help us understand the effects
of base sequences on the dynamics of folding pathways. Furthermore, we
are developing programs to automate the analysis of folding
pathways. This would enable us to detect the presence of several
structural processes given large amounts of structural
information.
DNA holds many exciting possibilities for nanomachines and
nanostructures. The challenge is to exercise absolute control over
construction procedures and make them rapid, scalable and reliable.
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