Peter G. Schultz (born June 23, 1956) is an American chemist. He is the CEO and Professor of Chemistry at
The Scripps Research Institute
Scripps Research, previously known as The Scripps Research Institute (TSRI), is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institu ...
, the founder and former director of
GNF, and the founding director of the California Institute for Biomedical Research (Calibr), established in 2012. In August 2014,
Nature Biotechnology
''Nature Biotechnology'' is a monthly peer-reviewed scientific journal published by Nature Portfolio. The chief editor heads an in-house team of editors. The focus of the journal is biotechnology including research results and the commercial busi ...
ranked Schultz the #1 top translational researcher in 2013.
Academic career
Schultz completed his undergraduate degree at
Caltech
The California Institute of Technology (branded as Caltech or CIT)The university itself only spells its short form as "Caltech"; the institution considers other spellings such a"Cal Tech" and "CalTech" incorrect. The institute is also occasional ...
in 1979 and continued there for his doctoral degree (in 1984) with
Peter Dervan. His thesis work focused on the generation and characterization of 1,1-diazenes and the generation of sequence-selective polypyrrole DNA binding/cleaving molecules. He then spent a year at the
Massachusetts Institute of Technology
The Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. Established in 1861, MIT has played a key role in the development of modern technology and science, and is one of the ...
with
Christopher Walsh before joining the chemistry faculty at the
University of California, Berkeley
The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public land-grant research university in Berkeley, California. Established in 1868 as the University of California, it is the state's first land-grant u ...
. He became a Principal Investigator of
Lawrence Berkeley National Laboratory
Lawrence Berkeley National Laboratory (LBNL), commonly referred to as the Berkeley Lab, is a United States Department of Energy National Labs, United States national laboratory that is owned by, and conducts scientific research on behalf of, t ...
in 1985 and an investigator of the
Howard Hughes Medical Institute
The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization based in Chevy Chase, Maryland. It was founded in 1953 by Howard Hughes, an American business magnate, investor, record-setting pilot, engineer, fil ...
in 1994.
In 1999 Schultz moved to
The Scripps Research Institute
Scripps Research, previously known as The Scripps Research Institute (TSRI), is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institu ...
and also became founding Director of the
Genomics Institute of the Novartis Research Foundation
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
(GNF), which was initiated purely as a genomic research outlet of Novartis, but which grew during Schultz's tenure to include a significant drug discovery effort and more than triple the number of intended employees (currently over 500 people). In March 2010, he left GNF to return to the non-profit sector and founded the California Institute for Biomedical Research (Calibr) in March 2012. He has trained over 300 graduate students and postdoctoral fellows, many of whom are on the faculties of major research universities.
[
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Research
Combinatorial chemistry and molecular evolution
Much of Schultz's work consists of finding ways to do a great many similar experiments at the same time, on many different compounds. He is one of the leading pioneers in combinatorial chemistry Combinatorial chemistry comprises chemical synthetic methods that make it possible to prepare a large number (tens to thousands or even millions) of compounds in a single process. These compound libraries can be made as mixtures, sets of individua ...
, screenable molecular libraries, and "high-throughput" chemistry. His interests are extremely wide-ranging, with applications in such diverse areas as catalytic mechanisms, cell-specialization and other complex biological processes (normally studied by biologists, not chemists), basic photochemistry, biophysical probes of all stripes from NMR through positron-emission, and solid-state materials science.
Early in his career Schultz showed that the natural molecular diversity of the immune system could be directed to generate catalytic antibodies. This method enabled the subsequent development of many new selective enzyme-like catalysts for reactions ranging from acyl transfer and redox reactions to pericyclic and metalation reactions. Although their catalytic activities are only rarely strong enough to be of practical use, catalytic antibodies have provided important new insights in our understanding of biocatalysis, structural plasticity of proteins, evolution of biochemical function, and the immune system itself.
Schultz then applied molecular diversity—the strategy of creating a large community of different molecules, plus a method for fishing out and identifying the ones that do what you want—to a range of problems in chemistry, biology and materials science. Along with Richard Lerner
Richard Alan Lerner (August 26, 1938 – December 2, 2021) was an American research chemist. Best known for his work on catalytic antibodies, Lerner served as President of The Scripps Research Institute (TSRI) until January 1, 2012, and was a ...
, he was one of the critical players in the development of phage-display libraries, and surface-library chips. For high-throughput bioassays which require freely soluble test-compounds, he uses microrobotic fluid-manipulation systems, adapted for 1,536-microwell cell-culture plates, to separately treat very small cell colonies with large numbers (hundreds of thousands) of different compounds.
Using these various high-throughput and combinatorial experimental approaches, Schultz has identified materials with novel optical, electronic, and catalytic properties; also, proteins and small molecules which control important biological processes such as aging, cancer, autoimmunity, and stem-cell differentiation and de-specialization back to pluripotency.
Unnatural amino acids
Schultz has pioneered a method for adding new building blocks, beyond the common twenty amino acids, to the genetic code
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
s of prokaryotic and eukaryotic organisms. This is accomplished by screening libraries of mutant amino acyl tRNA synthetase
An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its corresponding tRNA. It does so by catalyzing the transesterification of a specific cognate amino acid or its pre ...
s for mutants which charge nonsense-codon tRNA
Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...
s with the desired unnatural amino acid. The organism which expresses such a synthetase can then be genetically programmed to incorporate the unnatural amino acid into a desired protein in the usual way, with the nonsense codon now coding for the unnatural amino acid. Normally, the unnatural amino acid itself must be synthesized in the lab and supplied to the organism by adding it to the organism's growth medium. The unnatural amino acid must also be able to pass through the organism's cell membrane into the interior of the organism.
More than seventy unnatural amino acids have been genetically encoded in bacteria, yeast, and mammalian cells, including photoreactive, chemically reactive, fluorescent, spin-active, sulfated, pre-phosphorylated, and metal-binding amino acids. This technology allows chemists to probe, and change, the properties of proteins, ''in vitro'' or ''in vivo'', by directing novel, lab-synthesized chemical moieties specifically into any chosen site of any protein of interest.
A bacterial organism has been generated which biosynthesizes a novel, previously unnatural amino acid (p-aminophenylalanine) from basic carbon sources and includes this amino acid in its genetic code. This is the first example of the creation of an autonomous twenty-one-amino-acid organism.
Unnatural genetic information
Schultz's group has recently created bacteria whose chromosomes include unnatural DNA-bases, and bacteria whose chromosomes are hybrids which include both RNA and DNA.
Origins of mitochondria
In order to probe details of the traditionally accepted hypothesis that mitochondria originated when independent bacteria capable of respiratory (oxygen-dependent) metabolism took up residence inside host cells which had previously only been capable of fermentation (metabolism without using oxygen), and evolved to establish a symbiotic relationship with them, Schultz's group has created bacteria capable of surviving inside yeast cells and maintaining a symbiotic relationship with the host yeast cells by carrying out reactions which the yeast cells cannot catalyze without the bacteria. One goal of this work is to culture the yeast-bacteria hybrids and see whether the bacterial genome evolves to increase the mutual benefits of its chemical interactions with the host cells, as has happened with mitochondria over time.
Commercial activities
He is a founder of Affymax Research Institute, Symyx Technologies
Symyx Technologies, Inc. was a company that specialized in informatics and automation products. Symyx provided software solutions for scientific research, including Enterprise Laboratory Notebooks and products for combinatorial chemistry. The sof ...
, Syrrx, Kalypsys, Phenomix, Ilypsa, Ambrx, and Wildcat Discovery Technologies.
Publications and retractions
Schultz has authored around 500 papers.[''Curriculum Vitae'']
One of his papers in 2013 PNAS about making more stable antibodies was retracted, due to suspect data from co-author Shiladitya Sen:
* Retraction notice:
Two papers from his lab published in 2004, one in ''Science'' and one in ''Journal of the American Chemical Society'', were retracted in 2009, related to work in the Shultz lab by a postdoc, Zhiwen Zhang, on incorporating non-native glycosylated amino acids into proteins. Had it succeeded, this method could have become an essential tool for investigating the functions of carbohydrate attachments to proteins; however, the work could not be replicated, and when the lab went to find the relevant notebooks, they were missing. In the course of the investigation, Zhang received emails and phone calls blackmailing him, and at one point the person doing this wrote to several institutions and ''Science'' saying that he or she was going to commit suicide. The lab eventually identified the problem as a misunderstanding of the function of a key enzyme used in the experiments. The papers were:
* Retraction notice:
* Retraction notice:
Awards
Schultz is a member of the National Academy of Sciences, USA
The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
(1993), the Institute of Medicine of the National Academy of Sciences (1998).
*2019 Tetrahedron Prize
*2016 Heinrich Wieland Prize The Heinrich Wieland Prize is awarded annually by the Boehringer Ingelheim Foundation for outstanding research on biologically active molecules and systems in the areas of chemistry, biochemistry and physiology as well as their clinical importance. ...
*2015 Honorary doctorate from Yale University
Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the wo ...
*2013 The Laureate Chemistry for the Future Solvay Prize
*2006 ACS Arthur C. Cope Award
The Arthur C. Cope Award is a prize awarded for achievement in the field of organic chemistry research. It is sponsored by the Arthur C. Cope Fund, and has been awarded annually since 1973 by the American Chemical Society. It consists of $25,000, ...
*2003 Paul Ehrlich and Ludwig Darmstaedter Prize
The Paul Ehrlich and Ludwig Darmstaedter Prize is an annual award bestowed by the since 1952 for investigations in medicine. It carries a prize money of 120,000 Euro. The prize awarding ceremony is traditionally held on March 14, the birthday of N ...
*1995 honorary doctorate from Uppsala University
Uppsala University ( sv, Uppsala universitet) is a public university, public research university in Uppsala, Sweden. Founded in 1477, it is the List of universities in Sweden, oldest university in Sweden and the Nordic countries still in opera ...
, Sweden
Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic country located on ...
*1994 Wolf Prize
The Wolf Prize is an international award granted in Israel, that has been presented most years since 1978 to living scientists and artists for ''"achievements in the interest of mankind and friendly relations among people ... irrespective of natio ...
in Chemistry
*1990 ACS Award in Pure Chemistry
The American Chemical Society Award in Pure Chemistry is awarded annually by the American Chemical Society (ACS) "to recognize and encourage fundamental research in pure chemistry carried out in North America by young men and women." "Young" me ...
*1988 NSF Alan T. Waterman Award
The Alan T. Waterman Award, named after Alan Tower Waterman, is the United States's highest honorary award for scientists no older than 40, or no more than 10 years past receipt of their Ph.D. It is awarded on a yearly basis by the National Scien ...
References
External links
The Schultz group website at Scripps Research
{{DEFAULTSORT:Schultz, Peter G.
1956 births
Members of the United States National Academy of Sciences
Members of the National Academy of Medicine
Living people
American geneticists
21st-century American chemists
Scripps Research faculty
Wolf Prize in Chemistry laureates
Howard Hughes Medical Investigators
UC Berkeley College of Chemistry faculty