@article {106556, title = {Glycan processing in the Golgi: optimal information coding and constraints on cisternal number and enzyme specificity.}, journal = {Elife}, volume = {11}, year = {2022}, month = {2022 Feb 17}, abstract = {

Many proteins that undergo sequential enzymatic modification in the Golgi cisternae are displayed at the plasma membrane as cell identity markers. The modified proteins, called glycans, represent a molecular code. The fidelity of this glycan code is measured by how accurately the glycan synthesis machinery realises the desired target glycan distribution for a particular cell type and niche. In this paper, we construct a simplified chemical synthesis model to quantitatively analyse the tradeoffs between the number of cisternae, and the number and specificity of enzymes, required to synthesize a prescribed target glycan distribution of a certain complexity to within a given fidelity. We find that to synthesize complex distributions, such as those observed in real cells, one needs to have multiple cisternae and precise enzyme partitioning in the Golgi. Additionally, for fixed number of enzymes and cisternae, there is an optimal level of specificity (promiscuity) of enzymes that achieves the target distribution with high fidelity. The geometry of the fidelity landscape in the multidimensional space of the number and specificity of enzymes, inter-cisternal transfer rates, and number of cisternae, provides a measure for robustness and identifies stiff and sloppy directions. Our results show how the complexity of the target glycan distribution and number of glycosylation enzymes places functional constraints on the Golgi cisternal number and enzyme specificity.

}, issn = {2050-084X}, doi = {10.7554/eLife.76757}, author = {Yadav, Alkesh and Vagne, Quentin and Sens, Pierre and Iyengar, Garud and Rao, Madan} } @article {45431, title = {Cascade of transitions in molecular information theory}, journal = {Journal of Statistical Mechanics: Theory and Experiment}, volume = {Art No. 093402}, year = {2018}, month = {10/2018}, abstract = {

Biological organisms are open, adaptive systems that can respond to changes in environment in specific ways. Adaptation and response can be posed as an optimization problem, with a tradeoff between the benefit obtained from a response and the cost of producing environment-specific responses. Using recent results in stochastic thermodynamics, we formulate the cost as the mutual information between the environment and the stochastic response. The problem of designing an optimally performing network now reduces to a problem in rate distortion theory{\textemdash}a branch of information theory that deals with lossy data compression. We find that as the cost of unit information goes down, the system undergoes a sequence of transitions, corresponding to the recruitment of an increasing number of responses, thus improving response specificity as well as the net payoff. We derive formal equations for the transition points and exactly solve them for special cases. The first transition point, also called the coding transition, demarcates the boundary between a passive response and an active decision-making by the system. We study this transition point in detail, and derive three classes of asymptotic behavior, corresponding to the three limiting distributions of the statistics of extreme values. Our work points to the necessity of a union between information theory and the theory of adaptive biomolecular networks, in particular metabolic networks.

}, doi = {10.1088/1742-5468/aaddaa}, author = {Das, S G and Rao, Madan and Iyengar, Garud} } @article {20317, title = {Universal lower bound on the free-energy cost of molecular measurements.}, journal = {Phys Rev E}, volume = {95}, year = {2017}, month = {2017 Jun}, pages = {062410}, abstract = {

The living cell uses a variety of molecular receptors to read and process chemical signals that vary in space and time. We model the dynamics of such molecular level measurements as Markov processes in steady state, with a coupling between the receptor and the signal. We prove exactly that, when the signal dynamics is not perturbed by the receptors, the free energy consumed by the measurement process is lower bounded by a quantity proportional to the mutual information. Our result is completely independent of the receptor architecture and dependent on signal properties alone, and therefore holds as a general principle for molecular information processing.

}, issn = {2470-0053}, doi = {10.1103/PhysRevE.95.062410}, author = {Das, Suman G and Rao, Madan and Iyengar, Garud} }