Our cells depend on thousands of proteins and nucleic acids that function as tiny machines: molecules that build, fold, cut, destroy, and transport all of the molecules essential for life. My group is discovering how these molecular machines work, looking at interactions between individual atoms to understand how they activate gene expression, DNA replication, and small RNA biology.
In Leemor Joshua-Tor’s lab, researchers study the molecular basis of nucleic acid regulatory processes using the tools of structural biology and biochemistry. One such regulatory process is RNA interference (RNAi), in which a small double-stranded RNA triggers gene silencing. Joshua-Tor and her team offered critical insight when they solved the crystal structure of the Argonaute protein and identified it as the long-sought Slicer. They then went on to explore the mechanism of the slicing event. The structure of human Argonaute 2 (hAgo2) bound to a microRNA (miRNA) guide allowed Joshua-Tor and her colleagues to understand how mRNA is cleaved during RNAi. This year, members of the Joshua-Tor lab explored the function of a very similar protein, called Argonaute 1, that has no slicing ability, even though it is almost identical in structure to the slicing hAgo2. Using biochemical methods and mutational analysis, they were able to identify key parts of the protein that are required for slicing activity. The lab also studies the generation of PIWI-interacting RNAs (piRNAs), which serve to protect the genome of germ cells. With colleagues in the Hannon lab, Joshua-Tor’s team also determined the structure and function of Zucchini, a key nuclease in the initial generation of piRNAs in fruit flies. In other work, the lab is exploring the mechanisms of heterochromatin formation and gene silencing through the study of a protein complex called RNA-induced initiation of transcriptional gene silencing (RITS). Joshua-Tor is also well known for her work on the E1 helicase enzyme, which acts to unwind DNA strands during the DNA replication process.
Member of the National Academy of Sciences
Member of the American Academy of Arts and Sciences
2018 Mildred Cohn Award in Biological Chemistry, ASBMB
2014 ACE Women’s Network, New York, Women in Science and Education Leadership Award
Fellow of the American Association for the Advancement of Science (AAAS)
2007 Dorothy Crowfoot Hodgkin Award (Inaugural award), The Protein Society
1996 Beckman Young Investigator Award
The “ORC” twists, pinches, and dances around DNA
September 16, 2020
The Origin Recognition Complex (ORC) is a key piece of cellular machinery, fundamental to life, yet so far mysterious.
Replicating a genome starts with a twist, a pinch, and a bit of a dance
September 16, 2020
Researchers have their first high resolution look at how “ORC,” a human protein complex essential to life, moves.
How two CSHL programs adapted during the COVID-19 pandemic
July 16, 2020
Mikala Egeblad and David Micklos presented their work at the “Life Science Across the Globe” seminar series.
What do these scientist moms do? Ask their kids.
May 8, 2020
We asked the children of three scientists to describe their mother’s work. See what they had to say.
Cracking the case of the norovirus
February 6, 2020
A pervasive virus has evaded vaccine developers for decades. By getting a clear look at its protective shell, they may finally know how to defeat it.
Bridge to education
December 15, 2019
CSHL’s DNA Learning Center builds new bridges between unique science education and diverse groups.
One experiment: The shape of norovirus
October 25, 2019
Scientists at CSHL examine the structure of a norovirus under the cryo-electron microscope.
The world of Brianna Bibel, The Bumbling Biochemist
September 17, 2019
Brianna Bibel, a third-year graduate student at WSBS, is making ripples in the science community through her social media presence.
Cryo-EM illuminates intricate designs of noroviruses
June 11, 2019
Researchers reconstruct four different strains of the food-poisoning causing norovirus using the groundbreaking cryo-electron microscope.
Norovirus structures could help develop treatments for food poisoning
June 11, 2019
Researchers at CSHL used cryo-EM to reconstruct the structures of four different strains of human noroviruses, which cause food poisoning.