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Ruben Gonzalez Jr.: Molecular Visualizer

Associate Professor and Director of Graduate Studies, Department of Chemistry, Columbia University. Age 42

By | September 1, 2014

© DUSTIN FENSTERMACHERRuben Gonzalez Jr. worked his way through a chemistry degree at Florida International University (FIU) in Miami, first at a fast-food joint, then at a video store, where he eventually became assistant manager. Somehow, he also found time for science, spending his last three years in Stephen Winkle’s lab researching changes in the shape of DNA when it switches from a normal, right-handed helix to the opposite, left-handed form.

“I got lucky—hit the jackpot—[when] Ruben decided he wanted to work in my lab,” says Winkle, who knew Gonzalez as the student in his biochemistry class acing all of the tests.

Gonzalez had planned on becoming a high school chemistry teacher after college, but Winkle saw a different path for the young scientist and encouraged him to apply to graduate programs. In 1995, the pair were in San Francisco for a meeting of the Biophysical Society when Gonzalez got the news he’d been accepted into the University of California, Berkeley, where Winkle had done his own graduate work years earlier. They headed across the bay to meet Winkle’s former advisor, Ignacio “Nacho” Tinoco Jr., who immediately sold Gonzalez on RNA. “The idea that this molecule could carry the genetic information like DNA does, but could also fold into really complicated three-dimensional structures that could do chemistry like proteins . . . I fell in love with that idea,” Gonzalez recalls.

In Tinoco’s lab at Berkeley, Gonzalez studied RNA pseudoknots, the simplest known tertiary structure of RNA, consisting of two intertwined hairpin loops. Gonzalez solved the structure of a magnesium ion binding site in a pseudoknot from the mouse mammary tumor virus. He accomplished this by swapping out the magnesium ions, which help stabilize the structure but are not visible using nuclear magnetic resonance (NMR), replacing them with cobalt hexammine ions, which are NMR active.1 “I could actually see where the cobalt hexammine bound to the RNA and detect how it stabilized that particular structure,” says Gonzalez.

“He was not only smart, but he was ambitious and really cared about the science,” Tinoco says of Gonzalez.

Gonzalez went to Stanford University for a postdoc, working under RNA expert Joseph (Jody) Puglisi and physicist Steve Chu to develop single-molecule fluorescence tools that could aid in imaging ribosomes interacting with tRNA during protein translation.2 “[This was] the very first demonstration ever that one could study ribosomes and translation using single-molecule fluorescent approaches,” Gonzalez says.

In 2006, Gonzalez arrived at Columbia University, where he now oversees four postdocs, 11 graduate students, and one undergrad. Much of his group’s current work involves extending discoveries about translation in E. coli to the process in eukaryotes, with an eye toward human health and disease. Gonzalez also continues to innovate on the technological front, most recently by applying single-molecule field-effect transistors (smFET)—carbon nanotubes covalently bonded to the nucleic acids or proteins of interest that can help illuminate molecular structure—to the study of RNA, ribosomes, and translation.3

Gonzalez says he’s excited about how this new tool is going to allow him to dissect the process of translation at an ever-finer scale, in particular at much faster timescales, opening a window on how “ribosomes or other enzymes make decisions about correct or incorrect substrates.”  

References

  1. R.L. Gonzalez Jr., I. Tinoco Jr., “Solution structure and thermodynamics of a divalent metal ion binding site in an RNA pseudoknot,” J Mol Biol, 289:1267-82, 1999. (Cited 97 times)
  2. S.C. Blanchard et al., “tRNA dynamics on the ribosome during translation,” PNAS, 101:12893-98, 2004. (Cited 311 times)
  3. S. Sorgenfrei et al., “Label-free single-molecule detection of DNA-hybridization kinetics with a carbon nanotube field-effect transistor,” Nature Nanotechnology, 6:126-32, 2011. (Cited 111 times)

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September 16, 2014

Excerpt: “Much of his group’s current work involves extending discoveries about translation in E. coli to the process in eukaryotes, with an eye toward human health and disease.”

My comment: That sums up the frustration that other serious scientists must share when they hear pseudoscientific nonsense touted about mutations, natural selection, and the evolution of biodiversity. The pseudoscientists often cite Lenski’s experiments as proof of evolution. See: The Man Who Bottled Evolution. For contrast, serious scientists know that all organisms compete for sources of carbon that sustain the molecular mechanisms of life cycles. The results of that competition exemplify how biophysically-constrained nutrient-dependent protein biosynthesis and degradation in species from microbes to man link ecological variation to the nutrient-dependent RNA-mediated pheromone-controlled physiology of reproduction.

It has become clear that RNA-mediated events link ecological variation to nutrient-dependent amino acid substitutions that differentiate cell types.

Cell type differentiation in species is controlled by the metabolism of nutrients to species-specific pheromones. The pheromones control the species-specific physiology of reproduction, which leads to ecological adaptations (see for review Kohl, 2013). Meanwhile, those with no understanding of biologically-based cause and effect comment on mutations, natural selection, and the evolution of biodiversity as if an evolutionary event had ever been described that linked Darwin’s ‘conditions of life’ from ecological variation to ecological adaptation via mutations. (No evolutionary event = no evolution via mutations and natural selection.)

They display their ignorance, albeit anonymously, in discussion groups that might otherwise facilitate advances. Instead, the discussion groups facilitate the spread of pseudoscientific nonsense and other nonsense at a time when others make progress by ignoring evolutionary theory, which is what Dobzhansky (1964) suggested they do 50 years ago. “…the only worthwhile biology is molecular biology. All else is “bird watching” or “butterfly collecting.” Bird watching and butterfly collecting are occupations manifestly unworthy of serious scientists!”

What if serious scientist, like Ruben Gonzalez Jr., whose visions have enabled them to detail how the epigenetic landscape is linked to the physical landscape of DNA in organized genomes via RNA-mediated events, were still reporting the results of their experiments in terms of mutations and the evolution of morphological phenotypes? Could any perspective on RNA and dynamic nuclear organization or Combating Evolution to Fight Disease be used to make scientific progress under conditions of extreme ignorance displayed by theorists?

Did the pseudoscientists never think to ask a serious scientist about the RNA-mediated physiology of reproduction or the requirement for the concurrent ecological adaptations of morphological and behavioral phenotypes? How much longer can pseudoscientists continue to spread their ignorance before it leads to the death of us all?

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