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 BioE337, 2014 HW1 3 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 BioE337, 2014 HW1 4 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? BioE337, 2014 HW1 5 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. BioE337, 2014 HW1
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