NICOLE D. MARINO
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New Bolton Center Kennett Square, PA
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610-444-5800
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Ryan Hospital Philadelphia, PA
Emergencies:
215-746-8911
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215-746-8387
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NICOLE D. MARINO, B.A., Ph.D.

Assistant Professor, University of Pennsylvania School of Veterinary Medicine, Department of Pathobiology
Lab: Marino Lab

Research Areas: Bacteria, Phage, CRISPR-Cas, Infectious Disease
PubMed Link
Contact Information:
Hill Pavilion 316
380 South University Ave

Research Interests: The Marino lab explores the molecular mechanisms that bacteria use to block or interrupt phage infection and how phages overcome or evade these defenses.

Keywords: Bacteria, Phage, CRISPR-Cas, Arms Race

Research Details:

I. How do bacteria thwart phage infection?
Dozens of new bacterial anti-phage systems have recently been found. Many of these systems are homologs of key eukaryotic immune proteins, such as cGAS and gasdermins, which appear to have originated in prokaryotes. While some anti-phage defense systems target phage directly (e.g. Cas12), others trigger cell death or dormancy to abort the infection and prevent phage spread (e.g. CBASS). We are interested in exploring the molecular mechanisms these systems use to detect and thwart phage infection.



II. How do phages overcome multi-layered bacterial defense systems?
Many bacteria encode multiple anti-phage systems, and closely related strains can differ dramatically in their defense repertoire. However, it is unclear how phages overcome these multi-layered defenses to replicate and spread throughout the population. Although a few phage-encoded inhibitors and evasion strategies have been uncovered, it remains a mystery how phages overcome most defense systems. We will explore the dark matter of phage genomes to discover and characterize these evasion mechanisms.



Ongoing Projects:
(1) Determining how a phage-encoded anti-CRISPR triggers translation-dependent Cas12a mRNA destruction. (2) Adapting translation-dependent mRNA downregulation as a tool for gene regulation in prokaryotes and beyond. (3) Systematically identifying phage-encoded proteins that trigger or inhibit diverse bacterial defense systems. (4) Determining the mechanism of bacterial anti-phage defense systems that are broadly conserved in animals.

Marino, N. D., Brodsky, I. E. Immunology: NACHT domain proteins get a prokaryotic origin story Current Biology 33: R875-R878, 2023.

Marino, N. D. Phage against the machine: discovery and mechanism of type V anti-CRISPRs Journal of Molecular Biology 435: 168054, 2023.

Nicole, D. Marino, Alexander, Talaie, Héloïse, Carion, Matthew, C. Johnson, Yang, Zhang, Sukrit, Silas, Yuping, Li, Joseph, Bondy-Denomy Translation-dependent downregulation of Cas12a mRNA by an anti-CRISPR protein bioRxiv : 2022.11.29.518452, 2023.

Marino, N. D., Pinilla-Redondo, R., Bondy-Denomy, J. CRISPR-Cas12a targeting of ssDNA plays no detectable role in immunity Nucleic Acids Research 50: 6414-6422, 2022.

Marino, N. D., Pinilla-Redondo, R., Csorgo, B., Bondy-Denomy, J. Anti-CRISPR protein applications: natural brakes for CRISPR-Cas technologies Nature Methods 17: 471-479, 2020.

Pinilla-Redondo, R., Shehreen, S., Marino, N. D., Fagerlund, R. D., Brown, C. M., Sorensen, S. J., Fineran, P. C., Bondy-Denomy, J. Discovery of multiple anti-CRISPRs highlights anti-defense gene clustering in mobile genetic elements Nature Communications 11: 5652, 2020.

Marino, N. D., Panas, M. W., Franco, M., Theisen, T. C., Naor, A., Rastogi, S., Buchholz, K. R., Lorenzi, H. A., Boothroyd, J. C. Identification of a novel protein complex essential for effector translocation across the parasitophorous vacuole membrane of Toxoplasma gondii PLoS Pathogens 14: e1006828, 2018.

Naor, A., Panas, M. W., Marino, N., Coffey, M. J., Tonkin, C. J., Boothroyd, J. C. MYR1-dependent effectors are the major drivers of a host cell''s early response to toxoplasma, including counteracting MYR1-independent effects mBio 9: , 2018.

Marino, N. D., Zhang, J. Y., Borges, A. L., Sousa, A. A., Leon, L. M., Rauch, B. J., Walton, R. T., Berry, J. D., Joung, J. K., Kleinstiver, B. P., Bondy-Denomy, J. Discovery of widespread type I and type V CRISPR-Cas inhibitors Science 362: 240-242, 2018.

Marino, N. D., Boothroyd, J. C. Toxoplasma growth in vitro is dependent on exogenous tyrosine and is independent of AAH2 even in tyrosine-limiting conditions Experimental Parasitology 176: 52-58, 2017.

Franco, M., Panas, M. W., Marino, N. D., Lee, M. C., Buchholz, K. R., Kelly, F. D., Bednarski, J. J., Sleckman, B. P., Pourmand, N., Boothroyd, J. C. A novel secreted protein, MYR1, is central to toxoplasma''s manipulation of host cells mBio 7: e02231-15, 2016.

Coffey, M. J., Sleebs, B. E., Uboldi, A. D., Garnham, A., Franco, M., Marino, N. D., Panas, M. W., Ferguson, D. J., Enciso, M., O'Neill, M. T., Lopaticki, S., Stewart, R. J., Dewson, G., Smyth, G. K., Smith, B. J., Masters, S. L., Boothroyd, J. C., Boddey, J. A., Tonkin, C. J. An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell Elife 4: , 2015.

Shastri, A. J., Marino, N. D., Franco, M., Lodoen, M. B., Boothroyd, J. C. GRA25 is a novel virulence factor of Toxoplasma gondii and influences the host immune response 82: 2595-605, 2014.

B.A. (Biochemistry & Cell Biology, Classical Studies) Rice University, 2011

Ph.D. (Microbiology and Immunology) Stanford University, 2017

University of California, San Francisco (2017 to 2023)
Postdoctoral Fellow, Department of Microbiology and Immunology