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RIG-I-like receptors (RLRs), RIG-I, MDA5, and LGP2, are a family of innate immune receptors that recognize viral RNA in the cytoplasm and initiate antiviral responses including the induction of type I interferons and other pro-inflammatory cytokines. All three proteins have both an RNA helicase domain with ATPase activity and a C-terminal domain (CTD) which is responsible for RNA binding. RIG-I and MDA5 also have two tandem caspase activation and recruitment domains (CARDs) at the N-terminus which are involved in downstream signaling. To understand the structural basis of viral RNA recognition by the RLRs, especially RIG-I, we have performed extensive biochemical studies to determine the binding properties of RIG-I with different forms of RNA, including dsRNA with and without 5'-triphosphate (5'-ppp) groups, and 5'-ppp ssRNA. RIG-I CTD binds to these forms of RNA, and exhibits the highest affinity for 5'-ppp dsRNA. We also determined the crystal structures of RIG-I CTD in complex with dsRNA with and without 5'-ppp by X-ray crystallography. The structures showed that RIG-I recognizes the termini of the dsRNA and interacts with the two types of RNA in different orientations. By comparing these complex structures together with mutagenesis studies, we conclude that RIG-I CTD is a versatile binding module capable of recognizing different RNA ligands. Similar but partially differing sets of residues are involved in the recognition of dsRNA with and without 5'-ppp. Mutations of key residues at the RNA binding surface also abolished RIG-I signaling in cells. In order to compare the RIG-I/RNA interactions with other RLRs, we also determined the dsRNA binding surface of MDA5 CTD by NMR titration studies. MDA5 CTD has a similar binding surface to that of RIG-I CTD, however with slightly different surface electrostatic potentials which indicate different interactions with RNA. This may explain how MDA5 senses differing types of viruses compared to RIG-I. The current RIG-I activation model suggests that after stimulation by RNA binding, RIG-I undergoes an ATP-dependent conformational change, exposing the CARDs for downstream signaling. To understand the critical role that the helicase domain plays in RIG-I activation by structural approach, we also attempted to crystallize the dsRNA-bound helicase domain together with CTD.

Structures grown via self-assembly are a unique field in nanotechnology. The morphology of self-assembled structures is affected by the balance between kinetics and thermodynamics during growth. Hence structures with tailored morphologies and properties can be created with adjustments in growth conditions. In this thesis we study crystal nucleation and equilibration, for both real and model systems. The growth of thin bismuth films is investigated on three atomically flat surfaces; Mica, Molybdenum di Sulphide, and highly oriented pyrolitic graphite (HOPG). Films are grown under UHV conditions, and characterised using scanning electron microscopy and atomic force microscopy. For coverages of only a few monolayers, bismuth particles are found to aggregate into flat, isolated islands. Islands have characteristic heights and morphologies for each substrate. By altering the deposition flux and coverage, the island density and morphology can be manipulated. On HOPG substrates, planar islands grown at low flux are replaced by 1D structures at high temperature. These anisotopic structures result from an anisotropy in bond strengths at the crystal-vapour interface. Depositing Bi on HOPG substrates at low flux or high temperature conditions produces nanorods aligned (roughly) perpendicular to step edges on the graphite. The aspect ratios (ARs) of these 1D structures are found to increase as the deposition flux is lowered, or the substrate temperature is increased. The Arrhenius dependence of the AR is determined from experiment. A Kinetic Monte Carlo (KMC) model for high AR step-edge aggregates was developed, determining the likely growth mechanism for the nanorods. A scaling regime devised from the KMC results predicts the dependence of nanorod ARs on flux and temperature, and allows an estimation of the energy binding Bi dimers to the sides of nanorods. Thin films can also be grown via the self-assembly of atomic clusters. After deposition coalescence of clusters has implications for the film morphology, and properties. We use KMC simulations to investigate the coalescence of pairs of 3D atomic clusters (15000 to 130000 atoms in size) via lattice based surface diffusion. For early coalescence stages, the radius of the neck region connecting the two clusters is found to develop with a different powerlaw to classical theory. For later coalescence stages, when the nucleation of new atomic layers on facets of the cluster is required for further coalescence the temperature, cluster size, and cluster orientation all influence the coalescence. Equilibration times for clusters coalescing at high temperature are found to be limited by the dissociation of atomic layers.

Thesis (MSc)--University of Stellenbosch, 2006. / Bibliography. Also available via the Internet.

Thesis (M.S.)--Ohio University, August, 2001. / Title from PDF t.p.

Thesis (M.S.)--Oregon State University, 2009. / Printout. Includes bibliographical references (leaf 31). Also available on the World Wide Web.

Thesis (PhD) - Swinburne University of Technology, Faculty of Engineering and Industrial Sciences, Centre for Micro-Photonics, 2008. / Submitted for the degree of Doctor of Philosophy, Centre for Micro-Photonics, Faculty of Engineering and Industrial Sciences, 2008. Typescript. Bibliography: p. 104-118.

Thesis (Ph. D.)--Missouri University of Science and Technology, 2009. / Vita. The entire thesis text is included in file. Title from title screen of thesis/dissertation PDF file (viewed May 4, 2009) Includes bibliographical references (p. 103-113).

Thesis (Ph. D.)--University of Washington, 2008. / Vita. Includes bibliographical references (leaves 277-286).

Includes bibliographical references (p. 93-96).