An Introduction to Rule-based Modeling of Immune Receptor Signaling

Cells process external and internal signals through chemical interactions. Cells that constitute the immune system (e.g., antigen presenting cell, T-cell, B-cell, mast cell) can have different functions (e.g., adaptive memory, inflammatory response) depending on the type and number of receptor molecules on the cell surface and the specific intracellular signaling pathways activated by those receptors. Explicitly modeling and simulating kinetic interactions between molecules allows us to pose questions about the dynamics of a signaling network under various conditions. However, the application of chemical kinetics to biochemical signaling systems has been limited by the complexity of the systems under consideration. Rule-based modeling (BioNetGen, Kappa, Simmune, PySB) is an approach to address this complexity. In this chapter, by application to the Fc$\varepsilon$RI receptor system, we will explore the origins of complexity in macromolecular interactions, show how rule-based modeling can be used to address complexity, and demonstrate how to build a model in the BioNetGen framework. Open source BioNetGen software and documentation are available at http://bionetgen.org.Comment: 5 figure

Open/Closed String Topology and Moduli Space Actions via Open/Closed Hochschild Actions

In this paper we extend our correlation functions to the open/closed case. This gives rise to actions of an open/closed version of the Sullivan PROP as well as an action of the relevant moduli space. There are several unexpected structures and conditions that arise in this extension which are forced upon us by considering the open sector. For string topology type operations, one cannot just consider graphs, but has to take punctures into account and one has to restrict the underlying Frobenius algebras. In the moduli space, one first has to pass to a smaller moduli space which is closed under open/closed duality and then consider covers in order to account for the punctures

Open/closed string topology and moduli space actions via open/closed Hochschild actions

In this paper we extend our correlation functions to the open/closed case. This gives rise to actions of an open/closed version of the Sullivan PROP as well as an action of the relevant moduli space. There are several unexpected structures and conditions that arise in this extension which are forced upon us by considering the open sector. For string topology type operations, one cannot just consider graphs, but has to take punctures into account and one has to restrict the underlying Frobenius algebras. In the moduli space, one first has to pass to a smaller moduli space which is closed under open/closed duality and then consider covers in order to account for the punctures

Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4

The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 engages with SUMO chains on linked substrates and catalyses their ubiquitination, which targets substrates for proteasomal degradation. Here we use a segmental labelling approach combined with solution nuclear magnetic resonance (NMR) spectroscopy and biochemical characterization to reveal how RNF4 manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer