Bio-medical Research

 

Unlocking the Mechanism of tRNA Translocation Through the Ribosome Using Large-Scale Molecular Simulation

Karissa Sanbonmatsu, NMC Affiliated Research Scientist, LANL Staff Scientist

The ribosome is one of the largest and highly conserved molecular machines, whose function is essential to all life. Its operational principles, however, remain largely a mystery. Among the myriad of steps catalyzed by the ribosome during protein synthesis, translocation is considered the ‘holy grail’ by many. Translocation is an intrinsic property of the ribosome, involving complex conformational changes of the two ribosome subunits that move the mRNA and tRNA substrates by precisely three nucleotides in a unidirectional fashion. Recently, studies demonstrated that the majority of translocation occurs during head swivel. Understanding the connection between head swivel and mRNA/tRNA movement will unlock a key operational principle of translocation. While there is growing consensus that head swivel is crucial to translocation, a direct relationship between these conformational rearrangements and the translocation reaction coordinate is lacking. We will use closely integrated molecular simulation and single-molecule FRET imaging studies to bridge this gap. Development of Attenuated HCMV/HIV Vectors for an HIV/AIDS Vaccine.
 

AFRI STEC Coordinated Project: Developing Rapid Nucleic Acid-based Assay for the Detection and Characterization of E. Coli.

Harshini Mukundan, NMC Affiliate Researcher, LANL Staff Scientist
Alina Deshpande, NMC Affiliate Researcher, LANL Staff Scientist
Kiersten Lenz, UNM Student
Shiga toxin-producing E. coli (STEC) are a serious threat to our food supply and public health, causing more than 265,000 infections each year. NMC participates with UNM on a large USDA grant that seeks to understand how E. coli pathogens travel throughout the beef production process and how outbreaks occur.  The program seeks to find ways to prevent illness and improve the safety of our nation's food supply. The NMC/UNM team is applying LANL developed technology to develop and implement rapid detection technologies for pre-harvest, post-harvest and consumer environments. The team has developed a rapid nucleic acid-based assay for the detection and characterization of STEC in the beef chain. This assay is the multiplex oligonucleotide ligation-PCR (MOL-PCR) and unlike other ligation-based assays that require multiple steps, MOL-PCR consists of a single tube reaction.
 

CECI Supplement, HTVN106

Bette Korber, NMC Affiliate Researcher, LANL Staff Scientist
Elena Giorgi, Postdoctoral Research Associate, Los Alamos National Laboratory
This HIV Phase I vaccine trial is a human trial to test the immune response and safety of an HIV vaccine insert designed by Bette Korber at LANL. The vaccine antigen design is an attempt to contend with HIV's diversity. Korber has assisted with the statistical and analysis plan, designed testing reagents, and helped with the FDA approvals throughout the process. This project will evaluate the vaccine response in terms of the ability to cross react with different strains of HIV. 
 

Development of Spread-Deficient HCMV/HIV Vectors for a Prophylactic HIV Vaccine

Bette Korber, NMC Affiliate Researcher, LANL Staff Scientist
James Theiler, Laboratory Fellow, Los Alamos National Laboratory
The goal of this program is to support the preclinical development of an HIV vaccine carried in an HCV vector. This program is a collaboration with the Picker laboratory at the University of Oregon.We have developed computation tools to design HIV inserts for the unusual vector.
 

CAVIMC Neutralizing Antibody Core 2

Bette Korber, NMC Affiliate Researcher, LANL Staff Scientist
This program is in collaboration with Dr. David Montefiori at Duke University. Our role is to assist in the analysis of broadly neutralizing antibodies and antibodies with other functionalities against HIV variants,design reagent panels for global vaccine trials, and to help develop and analyze antibody reagents for therapy and prevention.
 

SEES Fellows: Modeling for Sustainability in a Changing Environment: Emerging Infectious Diseases

Carrie Manore
 
This project is studying the impact of changes in the environment upon the risks for emerging infectious diseases, and will create a hierarchy of multi-scale, integrative models incorporating nonlinear systems of differential equations, ecological networks, and agent-based models to provide a framework for understanding and mitigating risk of emerging infectious diseases in a spatially heterogeneous environment. The research will focus on a few emerging or potentially emerging infectious diseases in the United States, including West Nile virus, dengue, Rift Valley fever, hantavirus, Zika, and chikungunya.
 
This study aims to inform how emerging disease risk can be mitigated by sustainable management of the environment in order to better inform policy makers. This includes better planning of urban and agricultural expansion, more effective and efficient public health strategies, increased surveillance and data sharing, and informed choices about the environment and biodiversity.
 

 

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