Rhiju Das

Last updated
Rhiju Das
Born
Alma mater
Known for EteRNA
Awards
(1995)
Scientific career
Fields
Institutions Stanford University
Doctoral advisor
Other academic advisors David Baker
Website daslab.stanford.edu

Rhiju Das (born 1978 in Houston, Texas[ citation needed ]) is a computational biochemist and a professor of biochemistry and physics at Stanford University. Research in his lab seeks a predictive understanding of how RNA molecules and their complexes form molecular machines fundamental to life. [2]

Contents

Education

Das was trained as a physicist before switching to biochemistry. His undergraduate education was at Harvard, in physics, followed by master's research as a Marshall scholar at Cambridge University and University College London in experimental cosmology and molecular phylogenetics. He completed his Ph.D. in physics at Stanford University, supervised by Sebastian Doniach and Daniel Herschlag.

Career

Das was a Jane Coffin Childs postdoctoral fellow working on protein structure prediction with David Baker at the University of Washington. [3] He joined Stanford’s biochemistry department in 2009 and was promoted with tenure in 2016. He was selected to be a Howard Hughes investigator in 2021, [4] and co-founded the RNA design startup Inceptive that same year. [5]

Research

Das develops methods to simulate and computationally design RNA molecules as well as experimental methods to infer RNA structure from multidimensional chemical mapping measurements. [6] Integrating these efforts, Das directs the Eterna massive open laboratory, which integrates an internet-scale videogame with massively parallel experiments and machine learning. [7] The project aims to empower citizen scientists to invent medicine. [8]

In 2020, Das and his staff used the Eterna platform to investigate potentially shelf-stable RNA vaccines for COVID-19. [9] An interview with Das about this work was featured in an episode of Nova, "Decoding COVID-19", in May 2020. [10]

Das also is known for his work on demonstrating the application of cryo-electron microscopy to accelerate the structure determination of RNA. [11] He helped launch and served as an assessor for the first RNA category in the Critical Assessment of Structure Prediction in 2022. [12]

Related Research Articles

<span class="mw-page-title-main">Protein</span> Biomolecule consisting of chains of amino acid residues

Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity.

<span class="mw-page-title-main">Structural biology</span> Study of molecular structures in biology

Structural biology, as defined by the Journal of Structural Biology, deals with structural analysis of living material at every level of organization.

<span class="mw-page-title-main">Biophysics</span> Study of biological systems using methods from the physical sciences

Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations. Biophysical research shares significant overlap with biochemistry, molecular biology, physical chemistry, physiology, nanotechnology, bioengineering, computational biology, biomechanics, developmental biology and systems biology.

<span class="mw-page-title-main">Structural bioinformatics</span> Bioinformatics subfield

Structural bioinformatics is the branch of bioinformatics that is related to the analysis and prediction of the three-dimensional structure of biological macromolecules such as proteins, RNA, and DNA. It deals with generalizations about macromolecular 3D structures such as comparisons of overall folds and local motifs, principles of molecular folding, evolution, binding interactions, and structure/function relationships, working both from experimentally solved structures and from computational models. The term structural has the same meaning as in structural biology, and structural bioinformatics can be seen as a part of computational structural biology. The main objective of structural bioinformatics is the creation of new methods of analysing and manipulating biological macromolecular data in order to solve problems in biology and generate new knowledge.

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">Max Planck Institute of Biochemistry</span> Research institute in Martinsried, Germany

The Max Planck Institute of Biochemistry is a research institute of the Max Planck Society located in Martinsried, a suburb of Munich. The institute was founded in 1973 by the merger of three formerly independent institutes: the Max Planck Institute of Biochemistry, the Max Planck Institute of Protein and Leather Research, and the Max Planck Institute of Cell Chemistry.

<span class="mw-page-title-main">Biomolecular structure</span> 3D conformation of a biological sequence, like DNA, RNA, proteins

Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule of protein, DNA, or RNA, and that is important to its function. The structure of these molecules may be considered at any of several length scales ranging from the level of individual atoms to the relationships among entire protein subunits. This useful distinction among scales is often expressed as a decomposition of molecular structure into four levels: primary, secondary, tertiary, and quaternary. The scaffold for this multiscale organization of the molecule arises at the secondary level, where the fundamental structural elements are the molecule's various hydrogen bonds. This leads to several recognizable domains of protein structure and nucleic acid structure, including such secondary-structure features as alpha helixes and beta sheets for proteins, and hairpin loops, bulges, and internal loops for nucleic acids. The terms primary, secondary, tertiary, and quaternary structure were introduced by Kaj Ulrik Linderstrøm-Lang in his 1951 Lane Medical Lectures at Stanford University.

Nucleic acid structure prediction is a computational method to determine secondary and tertiary nucleic acid structure from its sequence. Secondary structure can be predicted from one or several nucleic acid sequences. Tertiary structure can be predicted from the sequence, or by comparative modeling.

<span class="mw-page-title-main">Eva Nogales</span> Biophysicist, professor

Eva Nogales is a Spanish-American biophysicist at the Lawrence Berkeley National Laboratory and a professor at the University of California, Berkeley, where she served as head of the Division of Biochemistry, Biophysics and Structural Biology of the Department of Molecular and Cell Biology (2015–2020). She is a Howard Hughes Medical Institute investigator.

<span class="mw-page-title-main">Molecular biophysics</span> Interdisciplinary research area

Molecular biophysics is a rapidly evolving interdisciplinary area of research that combines concepts in physics, chemistry, engineering, mathematics and biology. It seeks to understand biomolecular systems and explain biological function in terms of molecular structure, structural organization, and dynamic behaviour at various levels of complexity. This discipline covers topics such as the measurement of molecular forces, molecular associations, allosteric interactions, Brownian motion, and cable theory. Additional areas of study can be found on Outline of Biophysics. The discipline has required development of specialized equipment and procedures capable of imaging and manipulating minute living structures, as well as novel experimental approaches.

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

David Baker 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. The problem of protein structure prediction to which Baker has contributed significantly has now been largely solved by DeepMind using artificial intelligence. Baker 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.

<span class="mw-page-title-main">Foldit</span> 2008 video game

Foldit is an online puzzle video game about protein folding. It is part of an experimental research project developed by the University of Washington, Center for Game Science, in collaboration with the UW Department of Biochemistry. The objective of Foldit is to fold the structures of selected proteins as perfectly as possible, using tools provided in the game. The highest scoring solutions are analyzed by researchers, who determine whether or not there is a native structural configuration that can be applied to relevant proteins in the real world. Scientists can then use these solutions to target and eradicate diseases and create biological innovations. A 2010 paper in the science journal Nature credited Foldit's 57,000 players with providing useful results that matched or outperformed algorithmically computed solutions.

Experimental approaches of determining the structure of nucleic acids, such as RNA and DNA, can be largely classified into biophysical and biochemical methods. Biophysical methods use the fundamental physical properties of molecules for structure determination, including X-ray crystallography, NMR and cryo-EM. Biochemical methods exploit the chemical properties of nucleic acids using specific reagents and conditions to assay the structure of nucleic acids. Such methods may involve chemical probing with specific reagents, or rely on native or analogue chemistry. Different experimental approaches have unique merits and are suitable for different experimental purposes.

<span class="mw-page-title-main">Nucleic acid secondary structure</span>

Nucleic acid secondary structure is the basepairing interactions within a single nucleic acid polymer or between two polymers. It can be represented as a list of bases which are paired in a nucleic acid molecule. The secondary structures of biological DNAs and RNAs tend to be different: biological DNA mostly exists as fully base paired double helices, while biological RNA is single stranded and often forms complex and intricate base-pairing interactions due to its increased ability to form hydrogen bonds stemming from the extra hydroxyl group in the ribose sugar.

<span class="mw-page-title-main">EteRNA</span> 2010 browser-based video game

Eterna is a browser-based "game with a purpose", developed by scientists at Carnegie Mellon University and Stanford University, that engages users to solve puzzles related to the folding of RNA molecules. The project is supported by the Bill and Melinda Gates Foundation, Stanford University, and the National Institutes of Health. Prior funders include the National Science Foundation.

<span class="mw-page-title-main">Structure validation</span> Process of evaluating 3-dimensional atomic models of biomacromolecules

Macromolecular structure validation is the process of evaluating reliability for 3-dimensional atomic models of large biological molecules such as proteins and nucleic acids. These models, which provide 3D coordinates for each atom in the molecule, come from structural biology experiments such as x-ray crystallography or nuclear magnetic resonance (NMR). The validation has three aspects: 1) checking on the validity of the thousands to millions of measurements in the experiment; 2) checking how consistent the atomic model is with those experimental data; and 3) checking consistency of the model with known physical and chemical properties.

<span class="mw-page-title-main">Cryogenic electron microscopy</span> Form of transmission electron microscopy (TEM)

Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample solution is applied to a grid-mesh and plunge-frozen in liquid ethane or a mixture of liquid ethane and propane. While development of the technique began in the 1970s, recent advances in detector technology and software algorithms have allowed for the determination of biomolecular structures at near-atomic resolution. This has attracted wide attention to the approach as an alternative to X-ray crystallography or NMR spectroscopy for macromolecular structure determination without the need for crystallization.

mRNA vaccine Type of vaccine

An mRNAvaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine delivers molecules of antigen-encoding mRNA into immune cells, which use the designed mRNA as a blueprint to build foreign protein that would normally be produced by a pathogen or by a cancer cell. These protein molecules stimulate an adaptive immune response that teaches the body to identify and destroy the corresponding pathogen or cancer cells. The mRNA is delivered by a co-formulation of the RNA encapsulated in lipid nanoparticles that protect the RNA strands and help their absorption into the cells.

<i>Decoding COVID-19</i> 2020 PBS documentary film

Decoding COVID-19 is a 2020 American PBS documentary television film from the American TV series, NOVA, that was released on May 13, 2020. The documentary film examines the COVID-19 pandemic over its initial six months, from its beginning in the last months of 2019 in Wuhan, Hubei, China to May 2020.

References

  1. "OSSM alumnus on front lines of researching COVID-19 vaccine". www.ossmfoundation.org. May 22, 2020. Archived from the original on April 18, 2022. Retrieved on 18 April 2022.
  2. https://profiles.stanford.edu/rhiju-das Faculty profile
  3. https://www.dropbox.com/s/507ly1p2f25kojp/RhijuDas_CurriculumVitae.pdf?dl=0 CV
  4. "Three faculty announced as HHMI investigators". 23 September 2021.
  5. Toews, Rob. "A Wave Of Billion-Dollar Language AI Startups Is Coming". Forbes. Retrieved 2023-12-19.
  6. Cheng, Clarence Yu; Chou, Fang-Chieh; Kladwang, Wipapat; Tian, Siqi; Cordero, Pablo; Das, Rhiju (2 June 2015). "Consistent global structures of complex RNA states through multidimensional chemical mapping". eLife. 4: e07600. doi: 10.7554/eLife.07600 . PMC   4495719 . PMID   26035425.
  7. "RNA Game Lets Players Help Find a Biological Prize". The New York Times. 11 January 2011.
  8. Hotz, Robert Lee (3 May 2016). "Videogamers Are Recruited to Fight Tuberculosis and Other Ills". Wall Street Journal via www.wsj.com.
  9. Skarky, Brent (25 May 2020). "Oklahoman leading charge to find vaccine for COVID-19". KFOR-TV.
  10. Holt, Sarah (13 May 2020). "Decoding COVID-19". Nova . Decoding COVID-19.{{cite episode}}: Unknown parameter |agency= ignored (help)
  11. Kappel, Kalli; Zhang, Kaiming; Su, Zhaoming; Watkins, Andrew M.; Kladwang, Wipapat; Li, Shanshan; Pintilie, Grigore; Topkar, Ved V.; Rangan, Ramya; Zheludev, Ivan N.; Yesselman, Joseph D.; Chiu, Wah; Das, Rhiju (July 2020). "Accelerated cryo-EM-guided determination of three-dimensional RNA-only structures". Nature Methods. 17 (7): 699–707. doi:10.1038/s41592-020-0878-9. ISSN   1548-7105. PMC   7386730 . PMID   32616928.
  12. Das, Rhiju; Kretsch, Rachael C.; Simpkin, Adam J.; Mulvaney, Thomas; Pham, Phillip; Rangan, Ramya; Bu, Fan; Keegan, Ronan M.; Topf, Maya; Rigden, Daniel J.; Miao, Zhichao; Westhof, Eric (December 2023). "Assessment of three-dimensional RNA structure prediction in CASP15". Proteins: Structure, Function, and Bioinformatics. 91 (12): 1747–1770. doi: 10.1002/prot.26602 . ISSN   0887-3585. PMC   10841292 . PMID   37876231.