Loren Williams

Last updated
Loren Dean Williams
Loren Dean Williams.jpg
Born
Alma mater University of Washington, Duke University
Scientific career
FieldsBiophysics, biochemistry, astrobiology
Institutions Georgia Institute of Technology
Doctoral advisor Barbara Ramsay Shaw
Website https://ww2.chemistry.gatech.edu/~lw26/

Loren Dean Williams is a biophysicist, biochemist, astrobiologist, and professor in the School of Chemistry and Biochemistry at the Georgia Institute of Technology in Atlanta, Georgia. His research seeks to understand the structural basis for macromolecular reactions, from the role of nucleic acids as targets of chemotherapeutics to the ancestral biochemistry of the ribosome during the origin of life.

Contents

Biography

Williams was born in Seattle, Washington, and raised in Seattle, Corvallis, Oregon, and Winnipeg, Manitoba. His maternal grandmother was Alice Franklin Bryant, Seattle peace activist, political candidate, and author. [1] His mother, Imogene Bryant Williams, was a teacher and activist for environmental protection and labor rights. [2] [3] His father, Harvey Dean Williams, was a science educator and environmentalist. [4] Williams lives in Atlanta, Georgia with his wife Nidhi Williams. Their son, Justin Williams, is a PhD candidate in Molecular and Cell Biology at UC Berkeley.

Scientific training

As a chemistry undergraduate at University of Washington, Williams worked on porphyrin chemistry in the laboratory of Martin Gouterman and was a sprinter on the varsity track team. As a PhD student in physical chemistry at Duke University in the laboratory of Barbara Ramsay Shaw, he studied the mechanisms of base pairing of cytosine and guanine. He was an American Cancer Society Postdoctoral Fellow at Harvard Medical School in the laboratory of Irving Goldberg. He then joined the laboratory of Alexander Rich at MIT as a NIH Postdoctoral Fellow, where he specialized in DNA intercalation and structural characterization of interactions between anti-cancer drugs and DNA.

Georgia Tech

Williams joined the chemistry faculty at the Georgia Institute of Technology in 1992 and received a NSF CAREER Award in 1995. At Georgia Tech, Williams has mentored 25 PhD students and received numerous awards for excellence in mentorship, teaching, outreach, and advocating for improved accessibility. [5] From 2008 to 2015, he served as the director of the RiboEvo Center at Georgia Tech, part of the NASA Astrobiology Institute. He is currently director of the NASA-funded Center for the Origin of Life (COOL) at Georgia Tech [6] and a Co-Lead of the Prebiotic Chemistry and Early Earth Environment Consortium (PCE3 a NASA Research Coordination Network). [7] In 2021, he was elected Fellow of the International Society for the Study of the Origin of Life (ISSOL).

Research

“A Rash Investigator”: Cation interactions with DNA

At Georgia Tech, Williams' research group began studying the structural basis for interactions between DNA and cations. Williams and his students developed a model in which cations such as sodium and magnesium interact directly with DNA and influence DNA conformation through electrostatic interactions. [8] This model challenged Richard Dickerson's long-standing non-electrostatic DNA conformation model by suggesting that the peaks of electron density near DNA were cations instead of waters; in response, Dickerson termed Williams a “rash investigator”. [9] Subsequent studies have confirmed the direct role of cations in nucleic acid chemistry.

Origins of life and ancestral biochemistry

Evolution of the ribosome

Since 2008, Williams' research group has focused on understanding the extant ribosome across the tree of life and constructing models of ancestral ribosomes by combining biophysical chemistry, molecular biology and bioinformatics. [10] Information found in ribosomes from all three domain of life has allowed his laboratory to construct reaction coordinates for biopolymer evolution and the evolution of the ribosome. [10] [11]

Iron as an ancient cofactor

Williams and his group members have shown that under conditions of the ancient Earth, i.e., in the presence of ferrous iron and the absence of molecular oxygen, RNA has catalytic power that it lacks on the modern Earth. [12] [13] In collaboration with Jennifer Glass, they have shown that ferrous iron is an effective cofactor for the ribosome and other nucleic acid processing enzymes. [14]

Chemical evolution and mutualism

Williams seeks to apply biological principles to chemical sciences. In Williams’ formalism, RNA and protein are molecular symbionts and a cell is a consortium of molecules in mutualism relationships. [15]

Water and ancestral biochemistry

In collaboration with Moran Frenkel-Pinter, Williams and coauthors showed that 40% of 6,500 known biochemical reactions either make or destroy water, suggesting that water may have been involved in selecting the earliest biomolecules for life. [16]

Related Research Articles

<span class="mw-page-title-main">Nucleic acid</span> Class of large biomolecules essential to all known life

Nucleic acids are biopolymers, macromolecules, essential to all known forms of life. They are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is the ribose derivative deoxyribose, the polymer is DNA.

<span class="mw-page-title-main">Nucleolus</span> Largest structure in the nucleus of eukaryotic cells

The nucleolus is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of signal recognition particles and plays a role in the cell's response to stress. Nucleoli are made of proteins, DNA and RNA, and form around specific chromosomal regions called nucleolar organizing regions. Malfunction of nucleoli can be the cause of several human conditions called "nucleolopathies" and the nucleolus is being investigated as a target for cancer chemotherapy.

<span class="mw-page-title-main">Polymerase</span> Class of enzymes

A polymerase is an enzyme that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base-pairing interactions or RNA by half ladder replication.

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

Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid (DNA) are nucleic acids. Along with lipids, proteins, and carbohydrates, nucleic acids constitute one of the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA, RNA is found in nature as a single strand folded onto itself, rather than a paired double strand. 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">RNA world</span> Hypothetical stage in the early evolutionary history of life on Earth

The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence of this stage.

<span class="mw-page-title-main">Ribosome</span> Intracellular organelle consisting of RNA and protein functioning to synthesize proteins

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 (mRNA) 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 (rRNA) molecules and many ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.

<span class="mw-page-title-main">RNA polymerase</span> Enzyme that synthesizes RNA from DNA

In molecular biology, RNA polymerase, or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template.

<span class="mw-page-title-main">Ribozyme</span> Type of RNA molecules

Ribozymes are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonstrated that RNA can be both genetic material and a biological catalyst, and contributed to the RNA world hypothesis, which suggests that RNA may have been important in the evolution of prebiotic self-replicating systems. The most common activities of natural or in vitro-evolved ribozymes are the cleavage or ligation of RNA and DNA and peptide bond formation. For example, the smallest ribozyme known (GUGGC-3') can aminoacylate a GCCU-3' sequence in the presence of PheAMP. Within the ribosome, ribozymes function as part of the large subunit ribosomal RNA to link amino acids during protein synthesis. They also participate in a variety of RNA processing reactions, including RNA splicing, viral replication, and transfer RNA biosynthesis. Examples of ribozymes include the hammerhead ribozyme, the VS ribozyme, Leadzyme and the hairpin ribozyme.

<span class="mw-page-title-main">Leslie Orgel</span> British chemist

Leslie Eleazer Orgel FRS was a British chemist. He is known for his theories on the origin of life.

The history of molecular biology begins in the 1930s with the convergence of various, previously distinct biological and physical disciplines: biochemistry, genetics, microbiology, virology and physics. With the hope of understanding life at its most fundamental level, numerous physicists and chemists also took an interest in what would become molecular biology.

Threose nucleic acid (TNA) is an artificial genetic polymer in which the natural five-carbon ribose sugar found in RNA has been replaced by an unnatural four-carbon threose sugar. Invented by Albert Eschenmoser as part of his quest to explore the chemical etiology of RNA, TNA has become an important synthetic genetic polymer (XNA) due to its ability to efficiently base pair with complementary sequences of DNA and RNA. However, unlike DNA and RNA, TNA is completely refractory to nuclease digestion, making it a promising nucleic acid analog for therapeutic and diagnostic applications.

Steven Albert Benner has been a professor at Harvard University, ETH Zurich, and the University of Florida where he was the V.T. & Louise Jackson Distinguished Professor of Chemistry. In 2005, he founded The Westheimer Institute of Science and Technology (TWIST) and the Foundation For Applied Molecular Evolution. Benner has also founded the companies EraGen Biosciences and Firebird BioMolecular Sciences LLC.

mRNA display

mRNA display is a display technique used for in vitro protein, and/or peptide evolution to create molecules that can bind to a desired target. The process results in translated peptides or proteins that are associated with their mRNA progenitor via a puromycin linkage. The complex then binds to an immobilized target in a selection step. The mRNA-protein fusions that bind well are then reverse transcribed to cDNA and their sequence amplified via a polymerase chain reaction. The result is a nucleotide sequence that encodes a peptide with high affinity for the molecule of interest.

<span class="mw-page-title-main">Gustavo Caetano-Anolles</span>

Gustavo Caetano-Anollés is Professor of Bioinformatics in the Department of Crop Sciences, University of Illinois at Urbana-Champaign. He is an expert in the field of evolutionary and comparative genomics.

<span class="mw-page-title-main">Abiogenesis</span> Natural process by which life arises from non-living matter

In biology, abiogenesis or the origin of life is the natural process by which life has arisen from non-living matter, such as simple organic compounds. The prevailing scientific hypothesis is that the transition from non-living to living entities on Earth was not a single event, but an evolutionary process of increasing complexity that involved the formation of a habitable planet, the prebiotic synthesis of organic molecules, molecular self-replication, self-assembly, autocatalysis, and the emergence of cell membranes. Many proposals have been made for different stages of the process.

Numerous key discoveries in biology have emerged from studies of RNA, including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article.

Roger Martin Wartell is the former Chair of the School of Biology, part of the College of Sciences at the Georgia Institute of Technology.

<span class="mw-page-title-main">Xeno nucleic acid</span>

Xeno nucleic acids (XNA) are synthetic nucleic acid analogues that have a different sugar backbone than the natural nucleic acids DNA and RNA. As of 2011, at least six types of synthetic sugars have been shown to form nucleic acid backbones that can store and retrieve genetic information. Research is now being done to create synthetic polymerases to transform XNA. The study of its production and application has created a field known as xenobiology.

In molecular biology, hybridization is a phenomenon in which single-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) molecules anneal to complementary DNA or RNA. Though a double-stranded DNA sequence is generally stable under physiological conditions, changing these conditions in the laboratory will cause the molecules to separate into single strands. These strands are complementary to each other but may also be complementary to other sequences present in their surroundings. Lowering the surrounding temperature allows the single-stranded molecules to anneal or “hybridize” to each other.

Jennifer B. Glass is a biogeochemist, geomicrobiologist, astrobiologist, and associate professor of biogeochemistry in the School of Earth and Atmospheric Sciences at the Georgia Institute of Technology in Atlanta, Georgia. Glass received the 2021 Thomas Hilker Award for Excellence in Biogeosciences from the American Geophysical Union. She was awarded the 2021 Alice C. Evans Award for Advancement of Women from the American Society of Microbiology.

References

  1. "Alice Franklin Bryant, war critic and author". The New York Times. 1977-06-10. ISSN   0362-4331 . Retrieved 2022-02-07.
  2. Wheeler, Tim (2020-07-01). "Imogene Williams, 89; A gentle soul with an iron will". People's World. Retrieved 2022-02-07.
  3. "These bus riders will change the way you think about commuting in Seattle". The Seattle Times. Retrieved 2022-02-07.
  4. "Remembering the life of Harvey Williams". obituaries.seattletimes.com. Retrieved 2022-02-07.
  5. "Williams Lab". ww2.chemistry.gatech.edu. Retrieved 2022-02-06.
  6. "COOL". cool.gatech.edu. Retrieved 2021-07-19.
  7. Gronstal, Aaron (2019). "New NASA Research Consortium To Tackle Life's Origins".
  8. McFail-Isom, Lori; Sines, Chad C; Williams, Loren Dean (1999). "DNA structure: cations in charge?". Current Opinion in Structural Biology. 9 (3): 298–304. doi:10.1016/s0959-440x(99)80040-2. ISSN   0959-440X. PMID   10361089.
  9. Chiu, Thang Kien; Kaczor-Grzeskowiak, Maria; Dickerson, Richard E. (1999). "Absence of Minor Groove Monovalent Cations in the Crosslinked Dodecamer C-G-C-G-A-A-T-T-C-G-C-G". Journal of Molecular Biology. 292 (3): 589–608. doi:10.1006/jmbi.1999.3075. PMID   10497024.
  10. 1 2 Holmes, Bob (2017). "The very first living thing is still alive inside each one of us". New Scientist. Retrieved 2021-08-01.{{cite web}}: CS1 maint: url-status (link)
  11. Petrov, Anton S.; Gulen, Burak; Norris, Ashlyn M.; Kovacs, Nicholas A.; Bernier, Chad R.; Lanier, Kathryn A.; Fox, George E.; Harvey, Stephen C.; Wartell, Roger M.; Hud, Nicholas V.; Williams, Loren Dean (2015). "History of the ribosome and the origin of translation". Proceedings of the National Academy of Sciences. 112 (50): 15396–15401. doi: 10.1073/pnas.1509761112 . ISSN   0027-8424. PMC   4687566 . PMID   26621738.
  12. Mohan, Geoffrey (2013). "RNA was a key ingredient in primordial soup that led to life". Los Angeles Times. Retrieved 2021-08-01.{{cite web}}: CS1 maint: url-status (link)
  13. Drahl, Carmen (2013). "Iron Makes RNA Catalyze An Additional Chemical Reaction". cen.acs.org. Retrieved 2021-08-01.{{cite web}}: CS1 maint: url-status (link)
  14. "Stripping the linchpins from the life-making machine reaffirms its seminal evolution: A daring experiment corroborates translational system's place at earliest foundations of life on Earth". ScienceDaily. Retrieved 2021-08-01.
  15. Lanier, Kathryn A.; Petrov, Anton S.; Williams, Loren Dean (2017). "The Central Symbiosis of Molecular Biology: Molecules in Mutualism". Journal of Molecular Evolution. 85 (1): 8–13. doi:10.1007/s00239-017-9804-x. ISSN   1432-1432. PMC   5579163 . PMID   28785970.
  16. Marshall, Michael (2021). "Water may be even more crucial to life than we thought". New Scientist. Retrieved 2022-02-06.