Karissa Sanbonmatsu

Last updated
Karissa Y. Sanbonmatsu
Karissa wikipedia2.jpg
Alma mater Columbia University
University of Colorado Boulder
University of Cambridge
Known for Structural Biology
First simulation of the ribosome
First million atom simulation
First simulation of a gene
First billion atom simulation
First structural study of a lncRNA
Quasilinear-Zakharov modeling
Awards Presidential Early Career Award for Scientists and Engineers
American Physical Society Fellow
Pembroke College Stokes Society Scientific Lecture Competition
Scientific career
Institutions Los Alamos National Laboratory
New Mexico Consortium
Thesis Competition between Langmuir wave-wave and wave-particle interactions in the auroral ionosphere
Doctoral advisor Martin V. Goldman

Karissa Y. Sanbonmatsu is an American structural biologist at Los Alamos National Laboratory. She works on the mechanism of non-coding RNA complexes including the ribosome, riboswitches, long non-coding RNAs, as well as chromatin. She was the first to perform an atomistic simulation of the ribosome, determine the secondary structure of an intact lncRNA and to publish a one billion atom simulation of a biomolecular complex. [1]

Contents

Education and early career

Sanbonmatsu was born in Rochester, New York, the daughter of Joan Loveridge-Sanbonmatsu, and Akira Loveridge-Sanbonmatsu, who are both professors of speech communication in the State University of New York. She attended Oswego High School, and was valedictorian. She won the Pembroke College Stokes Society Scientific Lecture Competition at the University of Cambridge. Sanbonmatsu studied physics at Columbia University, where she used the Very Large Array radio telescope to estimate the distance to supernova remnant G27.4+0.0 and its central X-ray source, [2] which is now known to be a magnetar. [3] [4] Karissa's early research was in plasma physics. She earned her PhD in astrophysical sciences at University of Colorado Boulder under Martin V. Goldman (a student of Donald F. Dubois). Her dissertation entailed analytical treatments of non-linear wave-wave interactions in plasmas, elucidating the competition between Langmuir wave-wave and wave-particle effects in the auroral ionosphere. [5] [6] [7] In 1997, after earning her doctorate, Sanbonmatsu joined Los Alamos National Laboratory as a postdoctoral scholar [4] [8] under Donald F. Dubois (a student of Murray Gell-Mann), determining the effect of kinetic processes on Langmuir waves in plasmas. [9] [10] She became interested in what distinguishes life from matter. [11] In 2002 Los Alamos built Q-machine, one of the world's fastest supercomputer. [11] The Q-machine allowed Sanbonmatsu to run the world's largest simulation in biology, publishing the first simulation of the ribosome in 2005, where she identified the “accommodation corridor” of the ribosome. [11] [12]

Research

The Sanbonmatsu Laboratory at Los Alamos National Laboratory was established in 2001. [4] They use a variety of wet lab and computational techniques to study ribosomes, long non-coding RNA (lncRNAs), riboswitches [13] [14] and chromatin. In 2005, Sanbonmatsu was awarded the Presidential Early Career Award for Scientists and Engineers. [15] At the time, epigenetics was beginning to develop, and Sanbonmatsu realised that RNA could be involved in how genes are turned on and off. [11]

Beginning in 2009, the Sanbonmatsu lab began releasing the Phenix/cryo_fit family of software in collaboration with many others. Built around the concept of native contact potential, it allows protein sequences to be fit to the 3D protein shape density determined by Cryo-Electron Microscopy. As cryo-EM overtook X-ray crystallography as the most widely used method for determining protein structure, the lab published 20 articles in 10 years implementing different software versions, many cited hundreds of times each. The software was used to determine the structure of Coronavirus spike protein and it's interaction with human ACE-2 to cause infection. [3]

Sanbonmatsu has also been a leading figure in structural studies of long non-coding RNAs in epigenetics. She studied COOLAIR, a stretch of RNA that controls the timing and flowering of plants. [16] It works by controlling the internal triggers that tell a plant to stop flowering, which work in combination with a repressor protein called Flowering Locus C. [16] When Sanbonmatsu studied the RNA structure, she found features that are similar to ribosomes. [16] In 2012 her group was the first to describe the secondary structure in a lncRNA; the steroid hormone receptor activator (SRA). [17] She went on to look at how the structure of RNA impacted the fate of a cell. [18] She uses illumina dye sequencing for high throughput SHAPE probing. [19]

The first billion atom simulation of an entire gene (GATA4). GATA4-structure.jpg
The first billion atom simulation of an entire gene (GATA4).

She develops computer simulations to understand tRNA translocation, combining single molecule fluorescence with cryogenic electron microscopy. Ribosomes undergo a dramatic change in structure when transfer RNA are passing through, and this was simulated computationally by Sanbonmatsu. [19] Sanbonmatsu has also written about gynandromorphism, and how DNA influences hormones, but hormone can reprogram DNA. [20] She was elected as a Fellow of the American Physical Society in 2012. [19] Most recently, her group set the record for the world's largest published biomolecular simulation at one billion atoms, the first simulation of an entire gene.

Public engagement

She described her work with epigenetics and came out as transgender in a 2014 TEDxTalk. [21] Sanbonmatsu delivered a TED talk at TEDWomen on The biology of gender, from DNA to the brain, in November 2018. [22] In the talk she covered epigenetics, how DNA can change due to trauma and diet, and how her gender transition led her to study the role of epigenetics in gender identity. Sanbonmatsu has served on the board of Equality New Mexico. [23]

Related Research Articles

<span class="mw-page-title-main">Messenger RNA</span> RNA that is read by the ribosome to produce a protein

In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.

<span class="mw-page-title-main">RNA</span> Family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself or by forming a template for the production of proteins. RNA and deoxyribonucleic acid (DNA) are nucleic acids. The nucleic acids constitute one of the four major macromolecules essential for all known forms of life. RNA is assembled as a chain of nucleotides. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

<span class="mw-page-title-main">Ribosome</span> Synthesizes proteins in cells

Ribosomes are macromolecular machines, found within all cells, that perform biological protein synthesis. Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA molecules and many ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.

<span class="mw-page-title-main">Epigenetics</span> Study of DNA modifications that do not change its sequence

In biology, epigenetics is the study of heritable traits, or a stable change of cell function, that happen without changes to the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic mechanism of inheritance. Epigenetics usually involves a change that is not erased by cell division, and affects the regulation of gene expression. Such effects on cellular and physiological phenotypic traits may result from environmental factors, or be part of normal development. Epigenetic factors can also lead to cancer.

The central dogma of molecular biology deals with the flow of genetic information within a biological system. It is often stated as "DNA makes RNA, and RNA makes protein", although this is not its original meaning. It was first stated by Francis Crick in 1957, then published in 1958:

The Central Dogma. This states that once "information" has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information here means the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein.

<span class="mw-page-title-main">Gene expression</span> Conversion of a genes sequence into a mature gene product or products

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, and ultimately affect a phenotype. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. The process of gene expression is used by all known life—eukaryotes, prokaryotes, and utilized by viruses—to generate the macromolecular machinery for life.

<span class="mw-page-title-main">Non-coding RNA</span> Class of ribonucleic acid that is not translated into proteins

A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as small RNAs such as microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs such as Xist and HOTAIR.

<span class="mw-page-title-main">Translation (biology)</span> Cellular process of protein synthesis

In biology, translation is the process in living cells in which proteins are produced using RNA molecules as templates. The generated protein is a sequence of amino acids. This sequence is determined by the sequence of nucleotides in the RNA. The nucleotides are considered three at a time. Each such triple results in addition of one specific amino acid to the protein being generated. The matching from nucleotide triple to amino acid is called the genetic code. The translation is performed by a large complex of functional RNA and proteins called ribosomes. The entire process is called gene expression.

<span class="mw-page-title-main">Regulation of gene expression</span> Modifying mechanisms used by cells to increase or decrease the production of specific gene products

Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products. Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.

<span class="mw-page-title-main">Ribosomal RNA</span> RNA component of the ribosome, essential for protein synthesis in all living organisms

Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal DNA (rDNA) and then bound to ribosomal proteins to form small and large ribosome subunits. rRNA is the physical and mechanical factor of the ribosome that forces transfer RNA (tRNA) and messenger RNA (mRNA) to process and translate the latter into proteins. Ribosomal RNA is the predominant form of RNA found in most cells; it makes up about 80% of cellular RNA despite never being translated into proteins itself. Ribosomes are composed of approximately 60% rRNA and 40% ribosomal proteins, though this ratio differs between prokaryotes and eukaryotes.

<span class="mw-page-title-main">EF-Tu</span> Prokaryotic elongation factor

EF-Tu is a prokaryotic elongation factor responsible for catalyzing the binding of an aminoacyl-tRNA (aa-tRNA) to the ribosome. It is a G-protein, and facilitates the selection and binding of an aa-tRNA to the A-site of the ribosome. As a reflection of its crucial role in translation, EF-Tu is one of the most abundant and highly conserved proteins in prokaryotes. It is found in eukaryotic mitochondria as TUFM.

<span class="mw-page-title-main">5S ribosomal RNA</span> RNA component of the large subunit of the ribosome

The 5S ribosomal RNA is an approximately 120 nucleotide-long ribosomal RNA molecule with a mass of 40 kDa. It is a structural and functional component of the large subunit of the ribosome in all domains of life, with the exception of mitochondrial ribosomes of fungi and animals. The designation 5S refers to the molecule's sedimentation coefficient in an ultracentrifuge, which is measured in Svedberg units (S).

<span class="mw-page-title-main">Prokaryotic large ribosomal subunit</span>

50S is the larger subunit of the 70S ribosome of prokaryotes, i.e. bacteria and archaea. It is the site of inhibition for antibiotics such as macrolides, chloramphenicol, clindamycin, and the pleuromutilins. It includes the 5S ribosomal RNA and 23S ribosomal RNA.

A double layer is a structure in a plasma consisting of two parallel layers of opposite electrical charge. The sheets of charge, which are not necessarily planar, produce localised excursions of electric potential, resulting in a relatively strong electric field between the layers and weaker but more extensive compensating fields outside, which restore the global potential. Ions and electrons within the double layer are accelerated, decelerated, or deflected by the electric field, depending on their direction of motion.

<span class="mw-page-title-main">EF-G</span> Prokaryotic elongation factor

EF-G is a prokaryotic elongation factor involved in mRNA translation. As a GTPase, EF-G catalyzes the movement (translocation) of transfer RNA (tRNA) and messenger RNA (mRNA) through the ribosome.

<span class="mw-page-title-main">Long non-coding RNA</span> Non-protein coding transcripts longer than 200 nucleotides

Long non-coding RNAs are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. This arbitrary limit distinguishes long ncRNAs from small non-coding RNAs, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs. Given that some lncRNAs have been reported to have the potential to encode small proteins or micro-peptides, the latest definition of lncRNA is a class of transcripts of over 200 nucleotides that have no or limited coding capacity. However, John S. Mattick and colleagues suggested to change definition of long non-coding RNAs to transcripts more than 500 nt, which are mostly generated by Pol II. That means that question of lncRNA exact definition is still under discussion in the field. Long intervening/intergenic noncoding RNAs (lincRNAs) are sequences of transcripts that do not overlap protein-coding genes.

<span class="mw-page-title-main">Eukaryotic ribosome</span> Large and complex molecular machine

Ribosomes are a large and complex molecular machine that catalyzes the synthesis of proteins, referred to as translation. The ribosome selects aminoacylated transfer RNAs (tRNAs) based on the sequence of a protein-encoding messenger RNA (mRNA) and covalently links the amino acids into a polypeptide chain. Ribosomes from all organisms share a highly conserved catalytic center. However, the ribosomes of eukaryotes are much larger than prokaryotic ribosomes and subject to more complex regulation and biogenesis pathways. Eukaryotic ribosomes are also known as 80S ribosomes, referring to their sedimentation coefficients in Svedberg units, because they sediment faster than the prokaryotic (70S) ribosomes. Eukaryotic ribosomes have two unequal subunits, designated small subunit (40S) and large subunit (60S) according to their sedimentation coefficients. Both subunits contain dozens of ribosomal proteins arranged on a scaffold composed of ribosomal RNA (rRNA). The small subunit monitors the complementarity between tRNA anticodon and mRNA, while the large subunit catalyzes peptide bond formation.

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

Nucleic acidquaternary structure refers to the interactions between separate nucleic acid molecules, or between nucleic acid molecules and proteins. The concept is analogous to protein quaternary structure, but as the analogy is not perfect, the term is used to refer to a number of different concepts in nucleic acids and is less commonly encountered. Similarly other biomolecules such as proteins, nucleic acids have four levels of structural arrangement: primary, secondary, tertiary, and quaternary structure. Primary structure is the linear sequence of nucleotides, secondary structure involves small local folding motifs, and tertiary structure is the 3D folded shape of nucleic acid molecule. In general, quaternary structure refers to 3D interactions between multiple subunits. In the case of nucleic acids, quaternary structure refers to interactions between multiple nucleic acid molecules or between nucleic acids and proteins. Nucleic acid quaternary structure is important for understanding DNA, RNA, and gene expression because quaternary structure can impact function. For example, when DNA is packed into heterochromatin, therefore exhibiting a type of quaternary structure, gene transcription will be inhibited.

Epigenetics of human development is the study of how epigenetics effects human development.

ncRNA therapy

A majority of the human genome is made up of non-protein coding DNA. It infers that such sequences are not commonly employed to encode for a protein. However, even though these regions do not code for protein, they have other functions and carry necessary regulatory information.They can be classified based on the size of the ncRNA. Small noncoding RNA is usually categorized as being under 200 bp in length, whereas long noncoding RNA is greater than 200bp. In addition, they can be categorized by their function within the cell; Infrastructural and Regulatory ncRNAs. Infrastructural ncRNAs seem to have a housekeeping role in translation and splicing and include species such as rRNA, tRNA, snRNA.Regulatory ncRNAs are involved in the modification of other RNAs.

References

  1. 1 2 Jung, Jaewoon; Nishima, Wataru; Daniels, Marcus; Bascom, Gavin; Kobayashi, Chigusa; Adedoyin, Adetokunbo; Wall, Michael; Lappala, Anna; Phillips, Dominic; Fischer, William; Tung, Chang-Shung; Schlick, Tamar; Sugita, Yuji; Sanbonmatsu, Karissa (17 April 2019). "Scaling molecular dynamics beyond 100,000 processor cores for large-scale biophysical simulations". Journal of Computational Chemistry. 40 (21): 1919–1930. doi:10.1002/jcc.25840. PMC   7153361 . PMID   30994934.
  2. ↑ Sanbonmatsu, K. Y.; Helfand, D. J. (1992-12-08). "A distance determination for the supernova remnant G27.4+0.0 and its central X-ray source". The Astronomical Journal. 104: 2189. Bibcode:1992AJ....104.2189S. doi: 10.1086/116393 .
  3. 1 2 Gao, Z. F.; Peng, Q. H.; Wang, N.; Yuan, J. P. (2012-11-09). "Magnetic field decay of magnetars in supernova remnants". Astrophysics and Space Science. 342 (1): 55–71. arXiv: 1312.2679 . Bibcode:2012Ap&SS.342...55G. doi:10.1007/s10509-012-1139-x. ISSN   0004-640X. S2CID   122752669.
  4. 1 2 3 "Keynotes - ACM SIGSOFT 2010 / FSE 18". fse18.cse.wustl.edu. Archived from the original on 2020-01-17. Retrieved 2019-04-11.
  5. ↑ Sanbonmatsu, K. Y.; Newman, D. L.; Goldman, M. V. (2001-06-01). "Quasi-linear Zakharov simulations of Langmuir turbulence at rocket altitudes in the auroral ionosphere". Journal of Geophysical Research: Space Physics. 106 (A6): 10519–10535. Bibcode:2001JGR...10610519S. doi: 10.1029/2000JA000270 .
  6. ↑ Sanbonmatsu, K. Y.; Doxas, I.; Goldman, M. V.; Newman, D. L. (1997-04-01). "Non-Markovian electron diffusion in the auroral ionosphere at high Langmuir-wave intensities". Geophysical Research Letters. 24 (7): 807–810. Bibcode:1997GeoRL..24..807S. doi: 10.1029/97GL00669 . S2CID   13831737.
  7. ↑ Sanbonmatsu, K. Y.; Goldman, M. V.; Newman, D. L. (1995-09-01). "Nonlinear coupling of lower hybrid waves to the kinetic low-frequency plasma response in the auroral ionosphere". Geophysical Research Letters. 22 (17): 2397–2400. Bibcode:1995GeoRL..22.2397S. doi:10.1029/95GL02227.
  8. ↑ Appel, Susanna (2017-08-29). "Fellows seminar series: New cryo-EM tools and new biochemical studies of long non-coding RNAs". SciLifeLab. Archived from the original on 2019-04-11. Retrieved 2019-04-11.
  9. ↑ Sanbonmatsu, K. Y.; Vu, H. X.; Bezzerides, B.; DuBois, D. F. (2000-05-02). "The effect of kinetic processes on Langmuir turbulence". Physics of Plasmas. 7 (5): 1723–1731. Bibcode:2000PhPl....7.1723S. doi:10.1063/1.873991. ISSN   1070-664X.
  10. ↑ Sanbonmatsu, K.; Vu, H.; DuBois, D.; Bezzerides, B. (1999-02-03). "New Paradigm for the Self-Consistent Modeling of Wave-Particle and Wave-Wave Interactions in the Saturation of Electromagnetically Driven Parametric Instabilities". Physical Review Letters. 82 (5): 932–935. Bibcode:1999PhRvL..82..932S. doi:10.1103/PhysRevLett.82.932. ISSN   0031-9007.
  11. 1 2 3 4 Giorgi, Elena E.; Photographer, ContributorScientist Writer (2016-02-15). "Decoding the Dark Matter of the Human Genome". HuffPost. Retrieved 2019-04-11.{{cite web}}: |first2= has generic name (help)
  12. ↑ Sanbonmatsu, K. Y.; Joseph, S.; Tung, C.-S. (2005-11-01). "Simulating movement of tRNA into the ribosome during decoding". Proceedings of the National Academy of Sciences. 102 (44): 15854–15859. Bibcode:2005PNAS..10215854S. doi: 10.1073/pnas.0503456102 . ISSN   0027-8424. PMC   1266076 . PMID   16249344.
  13. ↑ "Sanbonmatsu Team: Models". www.lanl.gov. Retrieved 2019-04-11.
  14. ↑ "Sanbonmatsu Team: People". www.lanl.gov. Retrieved 2019-04-11.
  15. ↑ Energy, Los Alamos National Laboratory, Operated by Los Alamos National Security, LLC, for the U. S. Department of. "Presidential Early Career Awards for Scientists and Engineers (PECASE)". www.lanl.gov. Retrieved 2019-04-11.{{cite web}}: CS1 maint: multiple names: authors list (link)
  16. 1 2 3 "New insights into 'plant memories'". ScienceDaily. Retrieved 2019-04-11.
  17. ↑ Chi, Kelly Rae (2016-01-20). "Finding function in mystery transcripts". Nature. 529 (7586): 423–425. Bibcode:2016Natur.529..423C. doi: 10.1038/529423a . ISSN   1476-4687. PMID   26791729.
  18. ↑ "Linking RNA structure and function". MIT News. 8 September 2016. Retrieved 2019-04-11.
  19. 1 2 3 "Research Objectives" (PDF). Research Features. Retrieved 2019-04-12.
  20. ↑ Weintraub, Karen (2019-02-25). "Split-Sex Animals Are Unusual, Yes, but Not as Rare as You'd Think". The New York Times. ISSN   0362-4331 . Retrieved 2019-04-12.
  21. ↑ Sanbonmatsu, Karissa (7 October 2014). "How You Know You're in Love: Epigenetics, Stress & Gender Identity". YouTube. Retrieved 13 April 2019.
  22. ↑ Sanbonmatsu, Karissa (10 January 2019), The biology of gender, from DNA to the brain , retrieved 2019-04-11
  23. ↑ "EQNM Board". Equality New Mexico. Retrieved 2021-05-29.

TED Talk - The biology of gender, from DNA to the brain

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