Brian A. Kuhlman is an American professor of biochemistry and biophysics at the UNC School of Medicine of University of North Carolina at Chapel Hill and a Sloan Research Fellow.
Kuhlman obtained Bachelor of Arts degree in chemical physics from Rice University in 1992. From 1993 to 1998 he studied under guidance of Daniel Raleigh to earn his Ph.D. in chemistry from Stony Brook University and from 1999 to 2002 he studied under guidance from David Baker to obtain Damon Runyon Postdoctoral Fellowship at the University of Washington. [1]
In 2003, Kuhlman designed the first full-domain artificial protein, Top7, with Gautam Dantas and other researchers, in David Baker's laboratory. In his independent research laboratory, Kuhlman continued pioneering research in protein design, including breakthroughs in protein interface design, design of protein loops, [2] stitching together components of natural proteins, [3] designed fusions for bispecific antibodies, [4] and progress toward vaccines. [5]
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.
A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit its development.
An HIV vaccine could be either a preventive vaccine or a therapeutic vaccine, which means it will either protect individuals from being infected with HIV or treat HIV-infected individuals. It could either induce an immune response against HIV or consist of preformed antibodies against HIV.
UMass Chan Medical School is a public medical school in Worcester, Massachusetts. It is part of the University of Massachusetts (UMass) system. It is home to three schools: the T.H. Chan School of Medicine, the Morningside Graduate School of Biomedical Sciences, and the Tan Chingfen Graduate School of Nursing, as well as a biomedical research enterprise and a range of public-service initiatives throughout the state.
Dengue virus (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus. Four serotypes of the virus have been found, a reported fifth has yet to be confirmed, all of which can cause the full spectrum of disease. Nevertheless, scientists' understanding of dengue virus may be simplistic, as rather than distinct antigenic groups, a continuum appears to exist. This same study identified 47 strains of dengue virus. Additionally, coinfection with and lack of rapid tests for zika virus and chikungunya complicate matters in real-world infections.
Protein design is the rational design of new protein molecules to design novel activity, behavior, or purpose, and to advance basic understanding of protein function. Proteins can be designed from scratch or by making calculated variants of a known protein structure and its sequence. Rational protein design approaches make protein-sequence predictions that will fold to specific structures. These predicted sequences can then be validated experimentally through methods such as peptide synthesis, site-directed mutagenesis, or artificial gene synthesis.
Epitope mapping is the process of experimentally identifying the binding site, or "epitope", of an antibody on its target antigen. Identification and characterization of antibody binding sites aid in the discovery and development of new therapeutics, vaccines, and diagnostics. Epitope characterization can also help elucidate the mechanism of binding for an antibody and can strengthen intellectual property (patent) protection. Experimental epitope mapping data can be incorporated into robust algorithms to facilitate in silico prediction of B-cell epitopes based on sequence and/or structural data. Epitopes are generally divided into three classes: linear, conformational and discontinuous. Linear epitopes are formed by a continuous sequence of amino acids in a protein. In Conformational epitopes the binding residues are contained within certain key protein structural conformations, such as in helices, loops or beta sheets. The conformation of the epitope is important for bringing binding residues in the correct positions. Finally, discontinuous epitopes consist of parts of the antigen that are not close in the protein sequence but are brought together by three-dimensional protein folding. Discontinuous epitopes can harbour linear and conformational parts. B-cell epitope mapping studies suggest that most interactions between antigens and antibodies, particularly autoantibodies and protective antibodies, rely on binding to discontinuous epitopes.
Rosetta@home is a distributed computing project for protein structure prediction on the Berkeley Open Infrastructure for Network Computing (BOINC) platform, run by the Baker laboratory at the University of Washington. Rosetta@home aims to predict protein–protein docking and design new proteins with the help of about fifty-five thousand active volunteered computers processing at over 487,946 GigaFLOPS on average as of September 19, 2020. Foldit, a Rosetta@home videogame, aims to reach these goals with a crowdsourcing approach. Though much of the project is oriented toward basic research to improve the accuracy and robustness of proteomics methods, Rosetta@home also does applied research on malaria, Alzheimer's disease, and other pathologies.
David Baker (born October 6, 1962 in Seattle, Washington is an American biochemist and computational biologist who has pioneered methods to predict and design the three-dimensional structures of proteins. He is the Henrietta and Aubrey Davis Endowed Professor in Biochemistry and an adjunct professor of Genome Sciences, Bioengineering, Chemical Engineering, Computer Science, and Physics at the University of Washington. He serves as the Director of the Rosetta Commons, a consortium of labs and researchers that develop biomolecular structure prediction and design software. He is a Howard Hughes Medical Institute investigator and a member of the United States National Academy of Sciences. He is also the director of the University of Washington's Institute for Protein Design.
A bispecific monoclonal antibody is an artificial protein that can simultaneously bind to two different types of antigen. Naturally occurring antibodies typically only target one antigen. BsMabs can be manufactured in several structural formats, and current applications have been explored for cancer immunotherapy and drug delivery.
Timothy "Tim" A. Springer, Ph.D. is an immunologist and Latham Family Professor at Harvard Medical School. Springer is best known for his pioneering work in discovering the first integrins and intercellular adhesion molecules (ICAMs) and elucidating how these cell adhesion molecules function in the immune system. His innovative use of monoclonal antibodies in his research paved the way for the development of therapeutic antibodies, known as selective adhesion molecule inhibitors, to treat autoimmune diseases. In recent years, Springer's research interest has expanded to include malaria, transforming growth factor beta (TGF-β) signaling molecules, and von Willebrand factor.
Charles Joel Arntzen is a plant molecular biologist.
ZMapp is an experimental biopharmaceutical drug comprising three chimeric monoclonal antibodies under development as a treatment for Ebola virus disease. Two of the three components were originally developed at the Public Health Agency of Canada's National Microbiology Laboratory (NML), and the third at the U.S. Army Medical Research Institute of Infectious Diseases; the cocktail was optimized by Gary Kobinger, a research scientist at the NML and underwent further development under license by Mapp Biopharmaceutical. ZMapp was first used on humans during the 2014 West Africa Ebola virus outbreak, having only been previously tested on animals and not yet subjected to a randomized controlled trial. The NIH ran a clinical trial starting in January 2015 with subjects from Sierra Leone, Guinea, and Liberia aiming to enroll 200 people, but the epidemic waned and the trial closed early, leaving it too statistically underpowered to give a meaningful result about whether ZMapp worked.
Akiko Iwasaki is the Waldemar Von Zedtwitz Professor in the Department of Immunobiology and a Professor in the Department of Molecular, Cellular, and Developmental Biology at Yale University. She is also a principal investigator at the Howard Hughes Medical Institute. Her research interests include innate immunity, autophagy, inflammasomes, sexually transmitted infections, herpes simplex virus, human papillomavirus, respiratory virus infections, influenza infection, T cell immunity, and commensal bacteria.
Raghavan Varadarajan is an Indian biophysicist and a professor at the Indian Institute of Science. He is known for his researches in the fields of protein structure and protein folding and his contributions in developing vaccines and drugs for treating a type of fatal influenza and HIV-1. He is a former J. C. Bose National Fellow of the Department of Science and Technology and an elected fellow of the Indian Academy of Sciences and the Indian National Science Academy. The Council of Scientific and Industrial Research, the apex agency of the Government of India for scientific research, awarded him the Shanti Swarup Bhatnagar Prize for Science and Technology, one of the highest Indian science awards, in 2002, for his contributions to biological sciences.
Gary J. Nabel, M.D., Ph.D, is an American virologist and immunologist, and President and Chief Executive Officer of ModeX Therapeutics in Natick, Massachusetts.
Bette Korber is an American computational biologist focusing on the molecular biology and population genetics of the HIV virus that causes infection and eventually AIDS. She has contributed heavily to efforts to obtain an effective HIV vaccine. She created a database at Los Alamos National Laboratory that has enabled her to design novel mosaic HIV vaccines, one of which is currently in human testing in Africa. The database contains thousands of HIV genome sequences and related data.
Kizzmekia "Kizzy" Shanta Corbett is an American viral immunologist. She is the Shutzer Assistant Professor at the Harvard Radcliffe Institute and assistant professor of immunology and infectious diseases at Harvard T.H. Chan School of Public Health. She joined Harvard following six years at the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases, National Institutes of Health based in Bethesda, Maryland. She earned a PhD in microbiology and immunology from the University of North Carolina at Chapel Hill in 2014. Appointed to the VRC in 2014, Corbett was the scientific lead of the VRC's Coronavirus Team, with research efforts aimed at propelling novel coronavirus vaccines, including a COVID-19 vaccine. In February 2021, Corbett was highlighted in the Time's "Time100 Next" list under the category of Innovators, with a profile written by Anthony Fauci.
Katherine Jane Doores is a British biochemist who is a senior lecturer in the School of Immunology & Microbial Sciences at King's College London. During the COVID-19 pandemic Doores studied the levels of antibodies in patients who had suffered from coronavirus disease.