Heads of Laboratories
Luciano Marraffini, Ph.D.
Laboratory of Bacteriology
Dr. Marraffini investigates the molecular mechanisms by which CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against viral and plasmid infections.
Sequence-directed genetic interference pathways control gene expression and preserve genome integrity in all kingdoms of life. In many bacteria and most archaea, clustered, regularly interspaced, short palindromic repeats (CRISPRs) specify a recently discovered genetic interference pathway that protects cells from viruses (phages) and conjugative plasmids. Within CRISPR sequences, the repeats are separated by short spacer sequences that match phage or plasmid genomes and specify the targets of interference. Spacer sequences are transcribed into CRISPR RNAs (crRNAs) — small RNAs that, through base-pairing interactions with the target sequence, guide Cas nucleases to the invasive nucleic acid. Upon infection, CRISPR arrays can acquire new repeat-spacer units that match the infecting phage or plasmid. Therefore, CRISPR-Cas systems provide adaptive and inheritable immunity to the bacterial cell. The spacer content of CRISPR arrays reflects the many different invaders encountered by the host and can be expanded rapidly in response to new ones. Accordingly, CRISPR loci constitute a “genetic memory” that ensures the rejection of new, returning and ever-present invading DNA molecules.
Dr. Marraffini uses Staphylococcus epidermidis and Streptococcus pyogenes as model systems for studying CRISPR immunity. The clinical isolate S. epidermidis RP62a harbors a CRISPR spacer that matches the nickase gene (nes) present in nearly all staphylococcal conjugative plasmids and prevents their spread. Using this system, Dr. Marraffini revealed that the CRISPR-Cas machinery targets DNA, rather than RNA, directly. Work in the Marraffini lab also demonstrated that the S. pyogenes crRNA-guided Cas9 DNA nuclease constitute a formidable tool for genetic engineering.
Dr. Marraffini’s current research employs molecular genetic and biochemical approaches to analyze the genesis and function of CRISPR-Cas systems. He ultimately hopes to answer fundamental questions about how CRISPR-Cas systems destroy their targets, how the genetic memory is generated and how CRISPR-Cas immunity affects the evolution of bacteria and archaea, particularly of bacterial pathogens. By performing detailed analyses of the underlying molecular mechanisms of CRISPR immunity, he hopes to facilitate the manipulation of this natural pathway to develop new technologies.
Dr. Marraffini, a native of Argentina, received his undergraduate degree from the University of Rosario in Argentina in 1998 and his Ph.D. from the University of Chicago in 2007, where he studied bacterial pathogenesis in the laboratory of Olaf Schneewind. He was a postdoc at Northwestern University from 2008 to 2010, when he joined Rockefeller as assistant professor.
He is a 2012 Rita Allen Foundation Scholar and a 2011 Searle Scholar and is the recipient of a 2012 NIH Director’s New Innovator Award, a 2010 RNA Society Award, a 2009 Nestle Award and a 2008 Jane Coffin Childs Memorial Fund for Medical Research fellowship.
Dr. Marraffini is a faculty member in the David Rockefeller Graduate Program, the Tri-Institutional M.D.-Ph.D. Program and the Tri-Institutional Ph.D. Program in Chemical Biology.
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