Brian Kuhlman

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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.

Contents

Early life

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.

Career

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 design of protein conformational switches, [1] 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]

Awards

Related Research Articles

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens. Antigen literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

<span class="mw-page-title-main">HIV vaccine development</span> In-progress vaccinations that may prevent or treat HIV infections

An HIV vaccine is a potential vaccine that could be either a preventive vaccine or a therapeutic vaccine, which means it would either protect individuals from being infected with HIV or treat HIV-infected individuals. It is thought that an HIV vaccine could either induce an immune response against HIV or consist of preformed antibodies against HIV.

<i>Indiana vesiculovirus</i> Species of virus

Indiana vesiculovirus, formerly Vesicular stomatitis Indiana virus is a virus in the family Rhabdoviridae; the well-known Rabies lyssavirus belongs to the same family. VSIV can infect insects, cattle, horses and pigs. It has particular importance to farmers in certain regions of the world where it infects cattle. This is because its clinical presentation is identical to the very important foot and mouth disease virus.

An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.

<span class="mw-page-title-main">Hemagglutinin (influenza)</span> Hemagglutinin of influenza virus

Influenza hemagglutinin (HA) or haemagglutinin[p] is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity.

<i>Dengue virus</i> Species of virus

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, and a reported fifth has yet to be confirmed, all of which can cause the full spectrum of disease. Nevertheless, the mainstream scientific community's 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.

<span class="mw-page-title-main">Top7</span>

Top7 is an artificial protein, classified as a de novo protein. This means that the protein itself was designed to have a specific structure and functional properties.

<i>In silico</i> Latin phrase referring to computer simulations

In biology and other experimental sciences, an in silico experiment is one performed on a computer or via computer simulation software. The phrase is pseudo-Latin for 'in silicon', referring to silicon in computer chips. It was coined in 1987 as an allusion to the Latin phrases in vivo, in vitro, and in situ, which are commonly used in biology. The latter phrases refer, respectively, to experiments done in living organisms, outside living organisms, and where they are found in nature.

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.

<span class="mw-page-title-main">Epitope mapping</span> Identifying the binding site of an antibody on its target antigen

In immunology, 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 binding mechanism of 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.

<span class="mw-page-title-main">Rosetta@home</span> BOINC based volunteer computing project researching protein folding

Rosetta@home is a volunteer computing project researching protein structure prediction on the Berkeley Open Infrastructure for Network Computing (BOINC) platform, run by the Baker lab. 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.

<span class="mw-page-title-main">David Baker (biochemist)</span> American biochemist and computational biologist (born 1962)

David Baker is an American biochemist and computational biologist who has pioneered methods to design proteins and predict their three-dimensional structures. He is the Henrietta and Aubrey Davis Endowed Professor in Biochemistry, an investigator with the Howard Hughes Medical Institute, and an adjunct professor of genome sciences, bioengineering, chemical engineering, computer science, and physics at the University of Washington. He was awarded the shared 2024 Nobel Prize in Chemistry for his work on computational protein design.

Malaria vaccines are vaccines that prevent malaria, a mosquito-borne infectious disease which affected an estimated 249 million people globally in 85 malaria endemic countries and areas and caused 608,000 deaths in 2022. The first approved vaccine for malaria is RTS,S, known by the brand name Mosquirix. As of April 2023, the vaccine has been given to 1.5 million children living in areas with moderate-to-high malaria transmission. It requires at least three doses in infants by age 2, and a fourth dose extends the protection for another 1–2 years. The vaccine reduces hospital admissions from severe malaria by around 30%.

<span class="mw-page-title-main">Antonio Lanzavecchia</span> Italian and Swiss immunologist

Antonio Lanzavecchia is an Italian and Swiss immunologist. As a fellow of Collegio Borromeo he obtained a degree with honors in Medicine in 1976 from the University of Pavia where he specialized in Pediatrics and Infectious Diseases. He is Head Human Immunology Program, Istituto Nazionale di Genetica Molecolare-INGM, Milan and SVP Senior research Fellow, Humabs/Vir Biotechnology, Bellinzona and San Francisco (USA). Since 2017, he is also Professor at the Faculty of Biomedical Sciences of the Università della Svizzera italiana (USI).

A bispecific monoclonal antibody is an artificial protein that can simultaneously bind to two different types of antigen or two different epitopes on the same antigen. Naturally occurring antibodies typically only target one antigen. BsAbs can be manufactured in several structural formats. BsAbs can be designed to recruit and activate immune cells, to interfere with receptor signaling and inactivate signaling ligands, and to force association of protein complexes. BsAbs have been explored for cancer immunotherapy, drug delivery, and Alzheimer's disease.

<span class="mw-page-title-main">GPRC5D</span> Protein-coding gene in the species Homo sapiens

G-protein coupled receptor family C group 5 member D is a protein that in humans is encoded by the GPRC5D gene. GPRC5D is a class C orphan Gprotein-coupled receptor predominantly expressed in multiple myeloma cells and hard keratinized tissues, with low expression in normal human tissues, rendering it an appealing target for multiple myeloma cells.

p24 capsid protein

The p24 capsid protein is the most abundant HIV protein with each virus containing approximately 1,500 to 3,000 p24 molecules. It is the major structural protein within the capsid, and it is involved in maintaining the structural integrity of the virus and facilitating various stages of the viral life cycle, including viral entry into host cells and the release of new virus particles. Detection of p24 protein's antigen can be used to identify the presence of HIV in a person's blood and diagnose HIV/AIDS, however, more modern tests have taken their place. After approximately 50 days of infection, the p24 antigen is often cleared from the bloodstream entirely.

<span class="mw-page-title-main">Bette Korber</span> American computational biologist

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.

<span class="mw-page-title-main">Kizzmekia Corbett</span> American immunologist

Kizzmekia "Kizzy" Shanta Corbett is an American viral immunologist. She is an Assistant Professor of Immunology and Infectious Diseases at Harvard T.H. Chan School of Public Health and the Shutzer Assistant Professor at the Harvard Radcliffe Institute since June 2021.

<span class="mw-page-title-main">EpiVacCorona</span> EpiVacCorona vaccine against COVID-19

EpiVacCorona is a peptide-based vaccine against COVID-19 developed by the Russian VECTOR Center of Virology. The lack of protective effectiveness of EpiVacCorona, which is still in use in Russia, has been reported in scientific literature and in the media. The vaccine consists of three chemically synthesized peptides that are conjugated to a large carrier protein. This protein is a fusion product of a viral nucleocapsid protein and a bacterial MBP protein. A phase III clinical trial to show whether or not the vaccine can protect people against COVID-19 was launched in November 2020 with more than three thousand participants. The conclusions and results of the trial have not been made public.

References

  1. Ambroggio, X.; et al. (2006). "Computational design of a single amino acid sequence that can switch between two distinct protein folds". J Am Chem Soc. 128 (4): 1154–61. doi:10.1021/ja054718w. PMID   16433531.
  2. Hu, X.; et al. (2007). "High-resolution design of a protein loop". Proc Natl Acad Sci U S A. 104 (45): 17668–73. Bibcode:2007PNAS..10417668H. doi: 10.1073/pnas.0707977104 . PMC   2077077 . PMID   17971437.
  3. "Frankenstein Proteins Stitched Together by Scientists". May 11, 2016. Retrieved August 13, 2019.
  4. Lewis, Steven M.; et al. (2014). "Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface". Nature Biotechnology. 32 (2): 191–8. doi:10.1038/nbt.2797. PMID   24463572. S2CID   10961481.
  5. "Researchers discover how body temperature wrecks potential dengue, Zika vaccine". ScienceDaily . May 18, 2018. Retrieved August 13, 2019.
  6. "Kuhlman wins DeLano Award for computer applications to enhance research". UNC Health Care. July 5, 2018. Retrieved August 13, 2019.
  7. "Brian Kuhlman, Ph.D., Protein Robotics: Making Science Fun while Improving Human Health". UNC Health Care. September 1, 2018. Retrieved August 13, 2019.