Peter Wright, PhD, is a distinguished Professor at the Department of Integrative Structural and Computational Biology at NECecil H. and Ida M. Green Investigator, renowned for his groundbreaking work in the field of protein structure, dynamics, and interactions. His laboratory employs cutting-edge techniques, primarily high-resolution nuclear magnetic resonance (NMR) spectroscopy, alongside other biophysical and biochemical methods, to unravel the complexities of protein behavior at a molecular level. Dr. Wright’s research is pivotal in understanding how proteins fold, function, and interact within biological systems.
Research Focus: Unveiling Protein Secrets Through NMR
Professor Wright’s research delves into the intricate world of proteins, focusing on three key areas:
Intrinsically Disordered Proteins and Cellular Signaling: A significant portion of Dr. Wright’s research is dedicated to intrinsically disordered proteins (IDPs). These proteins, prevalent in eukaryotes, are crucial players in cellular regulation and signaling pathways. His lab utilizes a multidisciplinary approach, integrating NMR spectroscopy, biochemical and biophysical techniques, and single-molecule fluorescence microscopy (in collaboration with Ashok Deniz). This comprehensive strategy aims to elucidate the structures of essential transcriptional coactivators like CBP and p300 and to map their interactions with viral and cellular targets. By employing innovative NMR methods, intein labeling technologies, and single-molecule FRET techniques, Dr. Wright’s team is pioneering the characterization of the structure and dynamics of IDPs and their complexes. Their work is shedding light on the mechanisms by which these disordered proteins adopt functional folds upon binding to their target molecules, a process critical for cellular communication and regulation.
Mechanisms of Protein Folding and Misfolding: Protein folding, the process by which a protein attains its functional three-dimensional structure, is fundamental to biology. Dr. Wright’s lab harnesses the unique capabilities of NMR to investigate the pathways of protein folding and misfolding. NMR spectroscopy provides unparalleled insights into the structural dynamics of unfolded states and transient, partially folded intermediates that occur during the folding process. Currently, his research is focused on applying NMR relaxation dispersion methods and real-time 19F NMR to dissect the molecular mechanism of transthyretin unfolding and aggregation. This protein misfolding is directly linked to amyloid diseases, and understanding this process is crucial for developing therapeutic interventions. Dr. Wright’s work offers a detailed view of the conformational changes proteins undergo during folding and misfolding, providing critical information for combating protein aggregation-related diseases.
Protein Dynamics and “Invisible” Excited States: Beyond static structures, proteins are dynamic entities, and their internal motions are essential for function, particularly in enzymes. Professor Wright’s research explores these dynamics, focusing on weakly populated, “invisible” excited states that play a functional role in enzyme catalysis. Using advanced NMR relaxation dispersion methods, his lab is characterizing the dynamics of the enzyme dihydrofolate reductase (DHFR) and determining the structures of these transient excited states. These innovative approaches are also being applied to study the dynamics of stress-activated protein kinases. These studies are providing unprecedented insights into the intrinsic dynamics of enzymes and their direct contributions to catalytic mechanisms, fundamentally advancing our understanding of enzyme function.
Education and Professional Journey
Dr. Wright’s academic journey reflects a deep and sustained commitment to chemistry and biophysics:
- Ph.D. (Chemistry), University of Auckland, 1972
- B.S. (Chemistry), University of Auckland, 1968
- M.S. (Chemistry), University of Auckland, 1969
His professional experience showcases a trajectory of leadership and impactful research contributions:
- 2013-Present: Professor, TSRI (The Scripps Research Institute)
- 1987-2012: Chair, TSRI
- 1984-1986: Professor, TSRI
- 1976-1984: Lecturer/Senior Lecturer, University of Sydney
- 1972-1976: Postdoctoral Fellow, University of Oxford
Awards and Recognition: A Testament to Scientific Excellence
Professor Wright’s contributions have been widely recognized through prestigious awards and honors, underscoring his impact on the scientific community:
- 2019: ISMAR Prize, International Society of Magnetic Resonance
- 2019: Akutsu Award, Korean Magnetic Resonance Society
- 2010: The Stein and Moore Award, The Protein Society
- 2010: Distinguished Scientist Award, San Diego Chapter, American Chemical Society
- 2009: Honorary Member, Israel Chemical Society
- 2008: Fellow, International Society of Magnetic Resonance (ISMAR)
- 2008: Member, The National Academy of Sciences
- 2008: Leach Medal
- 2006: Honorary Member, NMR Society of Japan
- 2003: Honorary Doctor of Science, The University of Sydney
- 1998: Fellow, American Association for the Advancement of Science
- 1995: Elected to the American Academy of Arts and Sciences
- 1995: Honorary Doctor of Medicine, Karolinska Institute, Stockholm
- 1994: NIH Merit Award, National Institutes of Health
- 1987: Endowed Chair, Cecil H. and Ida M. Green Investigator in Medical Research
- 1972: New Zealand University Grants Committee Postdoctoral Fellow, University of Oxford
- 1969: New Zealand University Grants Committee Post-Graduate Scholar
Selected Publications: High-Impact Research
Professor Wright’s research has been published in highly regarded scientific journals. A selection of his key publications includes:
- Berlow, R. B.; Dyson, H. J.; Wright, Peter E. Hypersensitive termination of the hypoxic response by a disordered protein switch. Nature 2017, 543, 447-451. [View]
- Krois, Alexander S.; Dyson, H. J.; Wright, Peter E. Long-range regulation of p53 DNA binding by its intrinsically disordered N-terminal transactivation domain. Proceedings of the National Academy of Sciences of the United States of America 2018, 115, E11302-E11310. [View]
- Sun, Xun; Dyson, H. Jane; Wright, Peter E. Kinetic analysis of the multistep aggregation pathway of human transthyretin. Proceedings of the National Academy of Sciences 2018, 115, 10040-10045. [View]
- Ferreon, Allan C.; Ferreon, Josephine C.; Wright, P E.; Deniz, Ashok A A. Modulation of allostery by protein intrinsic disorder. 2013, 498, 390-4.
- Sugase, K.; Dyson, H. J.; Wright, Peter E. Mechanism of coupled folding and binding of an intrinsically disordered protein. Nature 2007, 447, 1021-1025. [View]
- Boehr, David D.; McElheny, Dan; Dyson, H. Jane; Wright, Peter E. The Dynamic Energy Landscape of Dihydrofolate Reductase Catalysis. Science 2006, 313, 1638-1642. [View]
In conclusion, Peter Wright PhD is a leading figure in the study of protein dynamics and NMR spectroscopy. His extensive research, numerous accolades, and impactful publications highlight his significant contributions to our understanding of protein behavior and function in biological systems. His ongoing work continues to push the boundaries of biophysical chemistry and holds immense promise for future breakthroughs in medicine and biotechnology.
