Every time a cell divides, it must accurately copy its DNA. With 3 billion “letters” in the human genome, this is no small task. My studies reveal the many steps and molecular actors involved, as well as how errors in DNA replication are involved in diseases that range from cancer to rare genetic disorders.
Bruce Stillman’s lab studies the process by which DNA is copied within cells before they divide in two. Working with yeast and human cells, Stillman and colleagues have identified many of the cellular proteins that function at the DNA replication fork during the S phase, the portion of the cell-division cycle when DNA synthesis occurs. Among these proteins are those that facilitate the assembly of chromatin, the protein–DNA complexes that form the chromosomes. Current research focuses on the mechanism that initiates the entire process of DNA replication in eukaryotic cells. At the heart of this mechanism is a protein that binds to “start” sites on the chromosomes, called the Origin Recognition Complex, ORC. The Stillman lab is part of an ongoing collaboration that determined the cryo-EM structure of ORC proteins in complex with a group of proteins, called a helicase, that unwind DNA during replication. These images offer molecular insights into how the helicase is loaded onto DNA. Stillman’s research also focuses on the process by which duplicated chromosomes are segregated during mitosis. They found ORC at centrosomes and centromeres, structures that orchestrate chromosome separation during mitosis. At centromeres, ORC subunits monitor the attachment of duplicated chromosomes to the mitotic spindle that pulls the chromosomes apart when they are correctly aligned. Stillman’s team has discovered that mutations in the Orc1 protein alter the ability of ORC to regulate both DNA replication and centrosome duplication. These mutations have been linked to Meier–Gorlin syndrome, a condition that results in people with extreme dwarfism and small brain size, but normal intelligence.
- Canada Gairdner International Award (with John Diffley, 2019)
- American Association for Cancer Research, Elected Fellow of the AACR Academy (2019)
- Doctor of Science, (honoris causa), Clarkson University (2018)
- Science and Technology Award, City of Suzhou, China (2018)
- National Academy of Inventors, Elected Fellow (2016)
- Herbert Tabor Research Award, American Society for Biochemistry and Molecular Biology (2014)
- Australian Academy of Science, Elected Corresponding Member (2012)
- Louisa Gross Horwitz Prize, Columbia University (with Thomas Kelly; 2010)
- American Academy of Arts and Sciences, Elected Member (2008)
- Doctor of Science (honoris causa), University of Sydney (2008)
- Doctor of Science, (honoris causa), Long Island University (2007)
- Society of Surgical Oncology – American Cancer Society Basic Science Award and Lecture (2006)
- Curtin Medal for Excellence in Medical Research, Australian National University (2006)
- American Association for the Advancement of Science, Elected Fellow (2005)
- Alfred P. Sloan Prize, General Motors Cancer Research Foundation, (with Thomas Kelly; 2004)
- Doctor of Science (honoris causa), Stony Brook University (2002)
- Doctor of Humane Letters (honoris causa), Hofstra University (2001)
- Doctor of Science (honoris causa), New York Institute of Technology (2001)
- European Molecular Biology Organization, Associate Member (2001)
- American Academy of Microbiology, Elected Fellow (2000)
- National Academy of Sciences, Elected Foreign Associate (2000); Member as of 2013
- Order of Australia, AO (1999)
- Julian Wells Medal, Lorne Genome Conference, Australia (1994)
- The Royal Society (London), Elected Fellow (1993)
DNA Learning Center Nigeria opens to local students
October 16, 2020
A small university in Nigeria hosts Africa’s first DNA Learning Center and plans to serve hundreds of students with hands-on genetics instruction.
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.
CSHL President Bruce Stillman wins Heineken Prize
June 2, 2020
CSHL President and CEO Bruce Stillman wins the Heineken Prize for his work on eukaryotic DNA replication.
Bridge to education
December 15, 2019
CSHL’s DNA Learning Center builds new bridges between unique science education and diverse groups.
Scientists take action to prevent sexual harassment and bias
November 7, 2019
Scientists gathered at Banbury Center last year to discuss ways to prevent gender bias and sexual harassment in science.
Historic building—groundbreaking science
October 29, 2019
The Demerec building has been monumental in scientific history. Now, a $75 million renovation of this celebrated labspace will define CSHL’s future.
May 20, 2019
Current discoveries about DNA and human genome position CSHL scientists to make life-changing breakthroughs that will improve the human condition.
An essay from the President: Biology for the planet
May 16, 2019
CSHL plant scientists are looking for solutions to the biggest questions in agriculture as environments are reshaped by climate change.