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Dr. Niles Lehman
Dr. Niles Lehman

Professor of Chemistry

Ph.D.| University of California, Los Angeles, 1990

Postdoctoral Fellow | The Scripps Research Institute, 1990-1993

Postdoctoral Fellow | University of Oregon, 1993-1995

503-725-8769

niles@pdx.edu

 

 

Research Interests

My research is focused on the biochemical and genetic issues involved with the origins of life on the Earth. As an evolutionary biochemist, I am interested in applying the same principles that govern the changes over time in modern populations of organisms to the populations of molecules that comprised the "primordial soup" from which life self-organized some 4 billion years ago. A current scenario for the origins of life postulates a time when all metabolic and information-flow processes were carried out by RNA molecules, as opposed to today, when proteins and DNAs primarily hold these responsibilities. This hypothetical time is called the RNA World, and draws much support from the wide variety of catalytic RNAs (ribozymes) that have been discovered to date.

Our research has two central themes. One is the role of recombination in the RNA World, and the other is the role of divalent metal ions in ribozyme-directed catalysis. Regarding the former, we are interested in the advantages that recombination (the swapping of large blocks of genetic information) could have played during the advent of life. We are investigating both the benefits that recombination gives for the creation of new genetic diversity and the protection that recombination provides against the accumulation of deleterious mutations in an otherwise adapted population of RNA molecules. To these ends, we have engineered the Azoarcus group I intron to be an effective RNA recombinase: it can recombine RNA fragments to construct new RNA sequences, including hammerhead, ligase, group I ribozymes, and importantly, itself (Riley & Lehman, 2003; Hayden et al. 2005; Hayden & Lehman, 2006). We are also using continuous evolution in vitro (Wright & Joyce, 1998; Science 276: 614-617) to test how rapidly RNA populations build up deleterious mutations and how effective recombination can be in preventing this from happening.

Regarding the latter, our lab uses evolution in vitro ("evolution in a test tube") to mimic the evolutionary process as it occurs in natural populations to explore the range of divalent catalysis available to different ribozymes. We are interested in the biochemical modifications and adaptations required to coax Mg(II)-dependent ribozymes to use other metals such as Ca(II), Sr(II), and Zn(II). Some ribozymes are malleable in this regard, while others are not, and we are using evolution in vitro coupled with a variety of standard biochemical techniques to elucidate patterns in ribozymology (Burton & Lehman, 2006).

Recently, we have been working with UCLA and OHSU to use in-vitro selection to develop new anti-cancer drugs.

Representative Publications

  • Arsene S, Ameta S, Lehman N, Grittiths AD, Nghe P, (2018). Coupled catabolism and anabolism in autocatalytic RNA sets. Nucleic Acids Research in press.
  • Jayathilaka TS, Lehman N (2018). Spontaneous covalent self-assembly of the Azoarcus ribozyme from five fragmentsChemBioChem 19(3),217-220.
  • Yeates JAM, Nghe P, Lehman N (2017). Topological and thermodynamic factors that influence the evolution of small networks of catalytic RNA speciesRNA  23(7),1088-1096.
  • Mathis C, Ramprasad SN, Walker SI, Lehman N (2017). Prebiotic RNA network formation: A taxonomy of molecular cooperation. Life 7, 38.
  • Yeates JAM, Hilbe C, Zwick M, Nowak M, Lehman N (2016).  Dynamics of prebiotic RNA self-reproduction illuminated by chemical game theory. Proc. Natl. Acad. Sci. USA 113(18), 5030-5035.
  • Higgs PG & Lehman N (2015). The RNA world: molecular cooperation at the origins of life. Nature Reviews Genetics 16, 7-17.
  • Nghe P, Hordijk W, Kauffman SA, Walker SI, Schmidt FJ, Kimble H, Yeates JAM, Lehman N (2015). Prebiotic network evolution: Six key parameters. Molecular BioSystems 11, 3206-3217.
  • Vaidya N, Walker SI, Lehman N (2013). Recycling of informational units leads to selection of replicators in a prebiotic soup. Chemistry & Biology 20, 241-252.
  • Vaidya N, Manapat ML, Chen IA, Xulvi-Brunet R, Hayden EJ, Lehman N (2012). Spontaneous network formation among cooperative RNA replicators. Nature 491, 72-77.
  • Lehman N (2008). A recombination-based model for the origin and early evolution of genetic evolution. Chemistry & Biodiversity 5, 1707-1717.
  • Hayden EJ, von Kiedrowski G, Lehman N (2008). Systems chemistry on ribozyme self-construction: evidence for anabolic autocatalysis in a recombination network. Angew. Chem. Int. Ed. 47, 8424-8428.
  • Hayden EJ, Lehman N (2006). Self-assembly of a group I intron from inactive oligonucleotide fragments. Chemistry & Biology 13, 909-918.
  • Lehman N (2004). Assessing the likelihood of recurrence during RNA evolution in vitro. Artificial Life 10, 1-22.