Roya ZandiProfessorPhysics and Astronomy Dept royaz@ucr.edu(951) 827-2096
Physics virus assembly and maturation: Energetics and dynamics
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AWARD NUMBER
009449-003
FUND NUMBER
33401
STATUS
Active
AWARD TYPE
3-Grant
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AWARD EXECUTION DATE
12/7/2017
BEGIN DATE
12/15/2017
END DATE
11/30/2020
AWARD AMOUNT
$3,001
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Sponsor Information
SPONSOR AWARD NUMBER
SPONSOR
SPONSOR TYPE
FUNCTION
Organized Research
PROGRAM NAME
Proposal Information
PROPOSAL NUMBER
17050766
PROPOSAL TYPE
New
ACTIVITY TYPE
Basic Research
PI Information
PI
Zandi, Roya
PI TITLE
Other
PI DEPTARTMENT
Physics and Astronomy
PI COLLEGE/SCHOOL
College of Nat & Agr Sciences
CO PIs
Project Information
ABSTRACT
Nontechnical Summary
This award supports theoretical and computational research, and education at the interface of materials research and biology and is aimed to advance understanding of how RNA viruses assemble. They infect bacteria, plants, and animals among many other hosts, and with all degrees of severity. All viruses, from the simplest to the most complicated, are built from a protein shell called the capsid which protects the genetic materials (RNA or DNA) they contain. The focus of this project is on single stranded RNA viruses that under many circumstances readily assemble from solutions containing capsid proteins and genome molecules. Due to advances in experimental techniques that probe living and inanimate matter at the nanoscale, the number of experiments investigating the physical basis of self-assembly and maturation of viral particles are soaring. This research project involves applying the methods of elasticity theory, and statistical and polymer physics to develop a physical model to explain experiments related to the formation of different viruses. The PI will engage three related projects. The first is to understand the factors that contribute to the efficient assembly and stability of spherical viral particles. The PI will study how the shape of RNA or to be mathematically precise, RNA topology, affects the size, shape and stability of viral shells and how the capsid structure and charge density in turn influences the structure of the encapsulated RNA. The second project involves analyzing the structure of immature human immunodeficiency virus (HIV) shell built from protein subunits, packed with local hexagonal shape and surrounded by a lipid bilayer. An intriguing feature of the immature HIV-1 is the presence of small and large gaps, covering about 30% of the surface of the enclosing membrane. The origin of the gaps is not well understood. The PI will explore what physical properties of protein subunits give rise to the structures similar to the immature HIV shell. Finally, the last project is devoted to the process of maturation of the spherical immature HIV particles, which involves cleavage of HIV immature building blocks by a set of chemical reactions leading to the assembly of the intriguing HIV conical capsid. Through the understanding of the interplay of RNA shape and the way viral capsid structure emerges, this project will advance understanding of the process of self-assembly which shapes much of the biomolecular world as well as biomaterials and polymer-based materials.
Understanding the physical factors that influence the formation of virus particles is currently finding applications in nanotechnology, actuators, drug delivery and gene therapy and can play a vital role in the development of new anti-viral therapies. Furthermore, this project will contribute to the education of undergraduate and graduate students, and particularly to the training of the next generation of soft condensed matter, polymer, and biological physicists in a multidisciplinary environment. The PI will also organize an outreach program for young women middle school students.
Technical Summary
This award supports theoretical and computational research and education at the interface of material science, soft condensed matter physics and biology. This project involves the extension of recent progress in the statistical theory of soft matter to the physics of viruses, which corresponds to the long-standing charge over-compensation problem in the physics of polyelectrolytes, the controversies about the impact of annealing and pseudoknots on the adsorption of RNA to the oppositely charged wall, and the structure of macromolecules under confinement. The research is focused on the statistical mechanics of viral self-assembly, both in equilibrium and far from equilibrium. The self-assembly and maturation of virus particles will be studied through developing new computational and theoretical models. The self-consistent field theory of polyelectrolytes needs to be extended to consider self-interaction of RNA while confined in a viral shell. Of particular interest is how the free energy of viral particles is influenced by the topology of RNA while interacting with the positively charged N-terminal domain of capsid proteins. The PI and her group will investigate the impact of the thermodynamic parameters on the size and geometry of the assembly products with the aim to explain the phenomena of co-existence and polymorphism observed in many virus assembly experiments. The PI combines the equilibrium statistical theory and classical nucleation theory to study how kinetic barriers influence the final structure of capsids. In view of complexity of the physics, in additional to analytical calculations, the PI will perform a series of both Monte Carlo and Brownian dynamics computer simulations to explore both the equilibrium and kinetic aspects of viral self-assembly and maturation. The important questions to be addressed are: What physical considerations govern the maturation of HIV particles? and What determines the ratio of different assembled structures from a solution of capsid proteins and genome molecules? The PI and her team will invetigate the impact of changes in the mechanical properties of coat proteins after protease cleavage, resulting in the transformation of the immature HIV to the mature conical capsid.(Abstract from NSF)
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