BioE337: Living soft matter, HW1

BioE337: Living soft matter, HW1
Instructor: Manu Prakash
Due Monday Feb 3, 2014 before the start of class
Problem 1
Storing information in DNA, 10 points
In his latest state of the union address, president Obama briefly mentioned a new
project brewing up in the scientific community termed Brain Activity Map Project
or BAMP. The idea is to build a functional connectomics of complete neural circuits
(functional circuit diagrams with activity maps) of behaving live brain (including
humans). This is being pitched as the next big ambitious goal, and is based on a
proposal that was presented a couple of months before in a publication in Neuron:
The Brain Activity Map Project and the Challenge of Functional Connectomics, A.
Paul Alivisatos et al. Neuron 74, June 21, 2012.
You are the science advisor to president Obama, and you have been tasked to understand the feasibility of what is being proposed here. Specifically help Mr. Obama
understand the following:
(a) Do we have the information storage capacity (convention storage such as hard
drive space) to store every spike from every neuron in a human brain. Assume reasonable numbers for spiking frequency, continuous recording duration of one month
and size of a human brain?
(b) The project proposes an unusually creative approach of ”wireless” recording of
neural activity using tools from synthetic biology and ”DNA based information storage.” They propose that DNA polymerase could be used as spike sensors since their
error rates are dependent on cation concentration. Thus DNA molecules could be synthesized to record patterns of errors corresponding to the patterns of spikes in each
cell, encoded as a calcium-induced errors, serving something akin to a ”ticker-tape”
record of activity of the neuron. What is the native error rate of DNA polymerase?
Provide back of the envelope calculations to either support or discard this idea considering fluctuation of cation concentration per spike, spiking rate and rate of synthesis
of DNA. Provide either a positive or negative recommendation for this remarkable
idea based on your back of the envelope calculations (see figure for details of the
scheme).
(c ) Estimate the information storage capability of DNA and compare it to option
analyzed in first part above? Estimate the volume such a ”ticker tape” will occupy
in a cell for continuous recording at 100Hz for one month?
2
Figure 1: A voltage sensitive calcium channel influences the error rate of an engineered
DNA polymerase. X marks sites of mismatch between T in the template strand
(lower) and G new copy strand. Note that the polymerase and DNA is inside the
cell.
At the end of this calculation, it should become clear why we do not remember everything we experience as a human being :)
Problem 2
Complexity of cell lineages,10 points
Some organisms, such as nematodes and ascidians, have a remarkably precise pattern
of cell divisions in early development. One can map out the lineage of each cell, division by division, and see the same pattern and the same fate in every individualthe
pattern is so stereotyped that each cell can be individually named, as in this pedigree
of all of the cells in the first four divisions of the nematode embryo. Developmental
processes are thought to be highly complex, but there have been few attempts to
measure and compare such complexity across different groups of organisms.
a) Using lineage map of C. elegans as an inspiration; propose a Kolmogorov complexity measure for lineage maps in metazoans.
b) Describe how you would compute this complexity in a hypothetical lineage map
(choose a hypothetical simplified lineage map).
c) Propose another measure of topological complexity to capture ideas that Kolmogorov complexity would have missed.
d) Critically examine your proposal for measuring complexity in developmental processes using lineage maps. Put these observations in a biological context and zero
evolutionary force law.
Note: With wide field of view, high resolution light sheet microscopy, automated
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Figure 2: C. elegans lineage map for inspiration.
You can use a simpler
hypothetical lineage (made up map) for your calculations.
More details at
http://wormweb.org/celllineage. Image credit Nature MCB.
construction of lineage maps is becoming a reality. I wonder if some of these measures
would actually predict developmental complexity and what the trends would look like
if we could just look up a lineage map for any organism. See for more details:
Towards comprehensive cell lineage reconstructions in complex organisms using lightsheet microscopy, By Fernando Amat* and Philipp J. Keller, Develop. Growth Differ.
(2013)
Problem 3
Spatio-temporal patterns, 10 points
Physical systems are driven far from equilibrium they often produce complex structures (patterns) that can be aperiodic in both space and time. Although many of
these data sets are easily obtainable, characterizing them is a significant challenge
with no generalizable rules that can be applied on all data sets. To introduce the
idea of mapping simple quantitative measures to evolving data; consider a following
snapshot from a video of a Rayleigh Benard Convection Cell experiment (see you
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tube video below for the full movie).
Figure 3:
A typical spatio-temporal data set from Rayleigh Benard Convection Experiment.
Watch full video on youtube at:
http://www.youtube.com/watch?v=iWjncdR7vsg
a) Develop a measure of quantifying the evolving patterns in context of techniques
discussed in the class. Include compositional and topological complexity framework
to your ideas. We are not looking for a right or wrong answer here; so let your imagination run wild.
Problem 4
More than meets the eye, 5 points
Sometimes physical systems can be a little bit surprising. Consider Chladni’s figures
for example, generated by sand on a piece of plate vibrated by a pushing a violin bow
next to the plate.
Figure
4:
Chladni’s
figures.
See
http://www.youtube.com/watch?v=Qf0t4qIVWF4
video
on
youtube
at:
a) What generates these patterns? How would you describe the complexity of
these figures?
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b) Why, if I repeat the same experiment at the exact same frequency but now with
a fine dust, does the pattern suddenly change?
Best of luck.
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