About This Project
By crafting denovo complexes from rubisco, we intend to enhance carbon fixation efficiency and explore the influence of higher-order oligomers on enzyme activity. In addition by optimizing CO2 access to designer rubisco through the integration of proteins, like carbonic anhydrase, we can enhance rubisco's adaptability across different organisms, including bacteria, algae, and plants. Our groundbreaking research transcends the boundaries of carbon fixation, potentially reshaping the field.
Ask the ScientistsJoin The Discussion
What is the context of this research?
Rubisco is key for CO2 fixation and crop growth. Our knowledge is mostly centered around form I rubisco in photosynthetic organisms, overlooking other forms. However, the fastest known rubisco is a phylogenetically distinct form II rubisco(fast Galionella). I propose engineering these into higher states while keeping their kinetic benefits.
Fast Galionella’s native structure isn’t suited for photosynthetic life. Its higher-order symmetry is key for combining it with carbonic anhydrase to concentrate carbon. We aim to design new carbon fixation structures, expanding rubisco’s use without host-specific engineering. Modern techniques enable targeted engineering, offering new rubisco manipulation possibilities.
What is the significance of this project?
We aim to enhance CO2 capture by improving the rate of carbon fixation in plants and algae. Integrated into crop plants, growth rates could rise by up to 6X, addressing food shortages. With this acceleration, it would take approximately 1 month from seed to fruit, leading to an increase in agricultural carbon capture of up to 5GT (gigatons). In algae, large bioreactors or ocean phytoplankton mats could enhance photosynthesis, potentially capturing an increase of 10GT of carbon annually, fostering a sustainable future.
What are the goals of the project?
Our objective is to enhance our understanding of how quaternary structure influences enzymatic activity. We aim to achieve this by creating designer Rubiscos with novel oligomeric states, using computational modeling and experimental validation.
Our design strategy includes the development of both homo-oligomeric and hetero-oligomeric complexes. The successful designs will merge the catalytic advantages of fast-form II Rubiscos into a biologically compatible complex, better suited for photosynthetic life.
Furthermore, we plan to integrate select designs with enzymes like carbonic anhydrase. This integration aims to saturate the Rubisco with substrate, potentially enhancing its efficiency. Our work aims to advance enzyme design and photosynthesis research significantly.
Most of the budget goes to supporting the student working on the project, and the support staff required for the lab to run. There is also $25,000 allocated for genes to be ordered to test the designs.
In the span of one year, we propose to have 100 designs produced and tested as described in the Research section.
May 31, 2024
produce 100 designs computationally
Jun 30, 2024
have genes transformed into E. coli expression system
Dec 31, 2024
purify and test designer proteins for oligomeric state and kinetic activity
Meet the Team
Team BioOur team comprises Dr. Justin Siegel, an enzyme design expert at UC Davis; Dr. Patrick Shih, a synthetic biology specialist at UC Berkeley; and Alexander J. Kehl, a Ph.D. candidate at UC Davis with a focus on Rubisco structure and design. Together, their combined expertise forms a robust foundation for innovative research.
Alexander J. Kehl
Alexander J. Kehl has devoted his scientific career to applying physical sciences to plant biology, becoming an expert in the structure and design of Rubisco. His journey in scientific research began at Cornell during a summer NSF REU internship, where his work was later published in Nucleic Acids Research. His exceptional performance led to his acceptance into the Maximizing Access to Research Careers/Biology Scholars Advanced Research Program (MARC/BSHARP), a program designed to provide intensive research experience to exceptional undergraduate students projected to be leaders in their field.
Alexander received his BS from UC Davis in pharmaceutical chemistry with a minor in plant biology. He continued his education by pursuing his Ph.D. in biophysics at UC Davis, where he is co-mentored by Patrick Shih from the University of California, Berkeley, and Justin Siegel from the University of California, Davis.
So far in his Ph.D., Alexander’s work has been published in Science Advances and has been presented at RosettaCon, the Western Photosynthetic Conference, and a Keystone conference on Computational Design and Modeling of Biomolecules. Alexander’s unique interdisciplinary training makes him one of the few people in the world with the knowledge and technical skills to bring a project like this to fruition.
Dr. Justin Siegel is an Associate Professor at the University of California, Davis, with affiliations in the Department of Biochemistry, Chemistry, and the Genome Center. He is also the Faculty Director of the Innovation Institute for Food and Health.
Dr. Siegel’s passion for science, particularly enzyme design, stems from his interest in combining computational and experimental tools to develop a fundamental knowledge of enzyme catalysis and applying those principles to design novel proteins. His scientific focus is on the design and discovery of enzymes relevant to issues in modern society – from treating Celiac disease to biofuel production and food system sustainability.
Dr. Siegel earned his B.S. in Biochemistry from UC Davis in 2005 and his Ph.D. in Biomolecular Structure and Design from the University of Washington in 2011. His educational background, combined with his extensive research experience, makes him uniquely qualified to conduct research projects in this field.
Dr. Siegel has published extensively in scientific journals. He has co-invented more than 100 global patents and is a co-founder of over a dozen companies and organizations. In 2023 he was elected to the National Academy of Inventors.
His work has led to the discovery and engineering of enzymes to treat celiac disease, fight anthrax infections, catalyze novel chemistry never before observed in nature, fixate carbon, amplify human nutrition, and produce high-value chemicals as well as nutrients. This track record of achievement underscores his credibility and demonstrates his ability to deliver real scientific progress.
Dr. Patrick Shih is an Assistant Professor of Plant and Microbial Biology at UC Berkeley, the Director of Plant Biosystems Design at the Joint BioEnergy Institute, Faculty Scientist at the Lawrence Berkeley National Lab, and Assistant Director of Climate Innovation at the Innovative Genomics Institute. Dr. Shih’s passion for science, particularly Rubisco and synthetic biology, stems from his interest in developing synthetic biology approaches to enable complex engineering efforts in plant systems for applications in agriculture, sustainability, human health, and bioenergy. He is also interested in leveraging genomics and molecular biology to investigate how the evolution of early microbial metabolisms (e.g., photosynthesis) shaped our planet over geological timescales.
Dr. Shih earned his B.S. and B.A. from UC San Diego in 2008 and his Ph.D. from UC Berkeley in 2013. His educational background, combined with his extensive research experience, makes him uniquely qualified to conduct research projects in this field.
Dr. Shih’s contributions to the field have been recognized through various awards and honors including the Packard Fellowship, Alfred P. Sloan Fellowship, Lawrence Berkeley National Laboratory Director’s Award for Exceptional Early Scientific Career Achievement, Branco Weiss Fellowship, NIH K99 award, and Life Sciences Research Fellowship. His work on rubisco has been published in Nature Communications, Nature Plants, and PNAS, and Science Advances.
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