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Biology subjects

Iyengar, G.

Publications and source records attributed to Iyengar, G..

3 recordsLinked to original sources

Dynamic Flux Balance Analysis Game

Flux balance analysis (FBA) for microbial communities often assumes a global objective function that all species cooperatively maximize in addition to maximizing their own growth. Combining community FBA with dynamic FBA to understand the time course and steady states of communities typically entails discretizing time and solving a community FBA model at each time point, a time-intensive process. We propose a dynamic community FBA model where species compete for metabolites to grow off of without needing to cooperate to maximize a community-level objective. An efficient method for computing steady state community compositions is provided, as well as methods for determining the stability of a steady state community to perturbations in biomass and invasion by species outside the community. The model and methods are applied to a model of four E. coli mutants with elements of competition (for shared metabolites) and cooperation (via mutants being auxotrophic for metabolites exported by other mutants), as well as a nine-species gut microbiome model.

systems biology↗

Transient Kinetic Proofreading

We propose a new stochastic model for understanding the transient kinetic proofreading mechanism in a T-cell. Our model indicates that a stochastic version of absolute ligand discrimination is a consequence of the finite number of receptors on the cell surface; thus, pointing to receptor number control as being critical to T-cell activation. We propose four different metrics to characterize the performance of kinetic proofreading mechanisms. We explore the numerical experiments that explore the trade-offs between speed, specificity, sensitivity, and robustness of T-cell activation as a function of the model parameters. We also consider the impact of receptor clustering on these trade-offs.

immunology↗

Glycan processing in the Golgi - optimal information coding and constraints on cisternal number and enzyme specificity

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 quantitatively analyse the tradeoffs between the number of cisternae and the number and specificity of enzymes, in order to synthesize a prescribed target glycan distribution of a certain complexity. 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 of enzymes that achieves the target distribution with high fidelity. Our results show how the complexity of the target glycan distribution places functional constraints on the Golgi cisternal number and enzyme specificity.

biophysics↗