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THE QIMRON LAB

Exploring fundamental aspects of bacterial defense systems, our research delves into the intricacies of CRISPR-Cas. Beyond unraveling its mechanisms, we leverage this knowledge to combat antibiotic resistance and engineer sex biasing in mammalian progeny.

Our laboratory explores bacterial defense systems, with a focus on the adaptive immune system known as CRISPR-Cas. This intriguing system dynamically adjusts to shield prokaryotes from newly encountered phages by executing a targeted RNA-guided assault on their nucleic acids. Additionally, we investigate novel phage interactions with their bacterial hosts, with a specific emphasis on their interplay with defense systems like CRISPR-Cas. These fundamental inquiries seamlessly transition into projects dedicated to combatting antibiotic resistance and even manipulating the sex distribution of mammalian progeny.

PUBLICATIONS

An efficient, scarless, selection-free technology for phage engineering

Moran G. Goren, Tridib Mahata, Udi Qimron | RNA Biology, in press, 2023

Inhibition of Host Cell Division by T5 protein 008 (Hdi)

Tridib Mahata, Shahar Molshanski-Mor, Moran G. Goren, Miriam Kohen-Manor, Ido Yosef, Oren Avram, Dor Salomon, Udi Qimron | Microbiology Spectrum, in press, 2023

Highly Active CRISPR-Adaptation Proteins Revealed by a Robust Enrichment Technology

Ido Yosef, Tridib Mahata, Moran G. Goren, Or J. Degany,  Adam Ben-Shem, and U Qimron | Nucleic Acids Research, in press, 2023097

Characterization of antibiotic resistomes by reprogrammed bacteriophage-enabled functional metagenomics in clinical strains

Apjok G, Számel M, Christodoulou C, Seregi V, Vásárhelyi BM, Stirling T, Eszenyi B, Sári T, Vidovics F, Nagrand E, Kovács D, Szili P, Lantos II, Méhi O, Jangir PK, Herczeg R, Gálik B, Urbán P, Gyenesei A, Draskovits G, Nyerges Á, Fekete G, Bodai L, Zsindely N, Dénes B, Yosef I, Qimron U, Papp B, Pál C, Kintses B. | Nature Microbiology, 8(3):410-423, 2023

A novel phage mechanism for selective nicking of dUMP-containing DNA

 Mahata T, Molshanski-Mor S, Goren MG, Jana B, Kohen-Manor M, Yosef I, Avram O, Pupko T, Salomon D, and Qimron U. | Proc Natl Acad Sci U S A, 118(23):e2026354118, 2021

Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

A Munitz, L Edry-Botzer, M Itan, R Tur-Kaspa, D Dicker, D Markovitch, M Goren, M Mor, S Lev, T Gottesman, K Muhsen, D Cohen, M Stein, U Qimron, N Freund, Y Wine,  M Gerlic | Scientific Reports, 11(1):3461, 2021

Phage T7 DNA mimic protein Ocr is a potent inhibitor of BREX defence.

Isaev A, Drobiazko A, Sierro N, Gordeeva J, Yosef I, Qimron U, Ivanov NV, Severinov K. | Nucleic Acids Res., 48(13):7601-7602, 2020

A continuous evolution system for contracting the host range of bacteriophage T7

Holtzman T, Globus R, Molshanski-Mor S, Ben-Shem A, Yosef I, and Qimron U | Scientific Reports, 10(1):307, 2020

**Top 50 downloads in Microbiology section

A genetic system for biasing the sex ratio in mice

Yosef I, Edry-Botzer L, Globus R, Shlomovitz I, Munitz A, Gerlic M, and Qimron U | EMBO Reports, (8):e48269, 2019

News and Views by David Zarkower and Michael Smanski in EMBO Rep – same issue

PROJECTS

THE CRISPR-CAS SYSTEM

The CRISPR-Cas system thwarts phage growth by generating short RNA molecules, directing a cleavage complex to specific nucleic acids. Our research is dedicated to unraveling the mechanisms and molecular components of this captivating defense system. Our particular focus lies on the adaptation step, where the acquisition of new short molecules encoding the guides takes place.

BACTERIOPHAGES AS GENETIC TOOLS

Over billions of years, phages and their hosts have undergone intricate co-evolution. Our research delves into uncovering novel phage interactions with their hosts, aiming to identify potential targets for drug design and develop inhibitors for these targets. Additionally, we leverage phages as natural targets for the CRISPR-Cas system, aiding in the exploration of mechanisms and the development of innovative technologies. Furthermore, our work involves the design of phage particles capable of packaging and delivering DNA molecules to a diverse array of bacterial hosts, with the goal of targeting various pathogens.

REVERSING ANTIBIOTIC RESISTANCE OF PATHOGENS

Our research focuses on the development of genetic constructs aimed at curbing the transfer of drug resistance genes among pathogens. We employ counter-selection markers and leverage the CRISPR-Cas system against genetic elements carrying drug-resistance cassettes. This strategic approach is designed to mitigate the spread of multi-drug resistant pathogens, contributing to more effective resistance management.

 Our cutting-edge research group has achieved groundbreaking milestones in the study of sex biasing in mammals. Our pioneering work involves being the first group to successfully generate biased sex production toward females in mammals. Additionally, we are the first group to produce sexed sperm in vivo. As leaders in this field, we are dedicated to advancing scientific knowledge and contributing to transformative breakthroughs that redefine the possibilities of genetic research. These studies hold significant promise for the development of farm animals capable of producing progeny solely with the desired sex.

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