Biosketch

MD with honors, NYU 1959; internship at Yale, assistant residency at Vanderbilt; post-doctorals with MR Pollock, NIMR London, R. Hotchkiss, Rockefeller; Researcher at PHRI 1965-93, Directoer, 1982-92 NYUSOM1993-present; currently Recanati Family Professor of Science, Emeritus. Research; microbiology, mainly on staphylococcal pathobiology, including antibiotic resistance. Early studies on MRSA revealed that staphylococcal beta-lactamase can hydrolyze methicillin, albeit too slowly to be of clinical importance. Discovered staphylococcal plasmids, including those encoding resistance to penicillin and to several heavy metals. Developed molecular tools for the study of staphylococcal molecular genetics, and a scheme for the nomenclature of bacterial plasmids. Developed mathematical model of plasmid incompatibitlty; demonstrated that plasmid replication initiation proteins must be inactivated after a single use; discovered and characterized the agr system, a key global regulator of staphylococcal virulence, controlled by a quorum-sensing system which is activated by a small cyclic thiolactone peptide. Supervised Emmmanuelle Charpentier in the construction of a set of cloning vectors, now in world-wide use, and discovered a mobile pathogenicity island in the staphylococcal chromosome, now known as a SaPI, that encoded and disseminated toxic shock toxin. SaPIs turned out to be very widespread in staphylococci and to have a major role in horizontal gene transfer.

Research Interests

The entire Novick lab is now focussed on re-purposing the SaPIs as antibacterial agents, as an answer to rampant antibiotic resistance. SaPIs are ~15 kb chromosomal units that are induced by helper phages and packaged in small phage-like particles, yielding titers of ~10e9/ ml. Deletion of genes controlling capsid size has resulted in packaging in full-sized phage capsids, adding 30 kb of cloning capacity. Toxin genes have been replaced by antibacterial cargos, including genes for CRISPR/cas9, CRISPR/dcas9 and lysostaphin. The CRISPR derivatives were curative for murine infections; tests with lysostaphin-encoding derivatives are in progress, as is construction of derivatives containing different types of antibacterial modules. The modified SaPIs are known as antibacterial drones (ABDs). A key feature of the ABD system is the incorporation of 2 or more antibacterial modules in a single ABD genome in order to preclude resistance.

Membership Type

Member

Election Year

2006

Primary Section

Section 44: Microbial Biology

Secondary Section

Section 21: Biochemistry