Functional Genomics Platform

Intro

The Functional Genomics Platform at Whitehead Institute provides advice and reagents to researchers interested in implementing large-scale CRISPR/Cas9 screens in mammalian cells.

We use the CRISPR/Cas9 system to identify modulators of different cellular phenotypes, such as viability and the output of reporter systems.

The FGP is directed by Heather Keys, Ph.D.

Jonathan Weissman, Ph.D. is the faculty advisor for the FGP.

On this website, you can find more details about our work, our team, contact information, and protocols.

Work

We assist researchers at all stages of the screening process, including planning, implementation and validation of genetic screens:

• Experimental design
• sgRNA library design and propagation
• Virus preparation for optimization and screening
• Vector design
• Sequencing library preparation
• Data analysis
• Follow-up strategies

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Publications

• Zhang Y, Donaher JL, Das S, Li X, Reinhardt F, Krall JA, Lambert AW, Thiru P, Keys HR, Khan M, Hofree M, Wilson MM, Yedier-Bayram O, Lack NA, Onder TT, Bagci-Onder T, Tyler M, Tirosh I, Regev A, Lees J, Weinberg RA. Genome-wide CRISPR screen identifies PRC2 and KMT2D-COMPASS as regulators of distinct EMT trajectories that contribute differentially to metastasis. Nat Cell Biol 24, 554–564 (2022). https://doi.org/10.1038/s41556-022-00877-0. Epub 2022 Apr 11. PubMed PMID: 35411083.
• Keys HR, Knouse KA. A genome-wide screen in the mouse liver reveals sex-specific and cell non-autonomous regulation of cell fitness. [preprint]. 2021 February. Available from: https://www.biorxiv.org/content/10.1101/2021.01.30.428976v1. doi: https://doi.org/10.1101/2021.01.30.428976.
• Rossiter NJ, Huggler KS, Adelmann CH, Keys HR, Soens RW, Sabatini DM, Cantor JR. CRISPR screens in physiologic medium reveal conditionally essential genes in human cells. Cell Metab. 2021 Jun 1;33(6):1248-1263.e9. doi: 10.1016/j.cmet.2021.02.005. Epub 2021 Mar 1. PubMed PMID: 33651980. PubMed Central PMCID: PMC8172426.
• Zou Y, Henry WS, Ricq EL, Graham ET, Phadnis VV, Maretich P, Paradkar S, Boehnke N, Deik AA, Reinhardt F, Eaton JK, Ferguson B, Wang W, Fairman J, Keys HR, Dančík V, Clish CB, Clemons PA, Hammond PT, Boyer LA, Weinberg RA, Schreiber SL. Plasticity of ether lipids promotes ferroptosis susceptibility and evasion. Nature. 2020 Sep;585(7826):603-608. doi: 10.1038/s41586-020-2732-8. Epub 2020 Sep 16. PubMed PMID: 32939090; PubMed Central PMCID: PMC8051864.
• Tsvetkov P, Detappe A, Cai K, Keys HR, Brune Z, Ying W, Thiru P, Reidy M, Kugener G, Rossen J, Kocak M, Kory N, Tsherniak A, Santagata S, Whitesell L, Ghobrial IM, Markley JL, Lindquist S, Golub TR. Mitochondrial metabolism promotes adaptation to proteotoxic stress. Nat Chem Biol. 2019 Jul;15(7):681-689. doi: 10.1038/s41589-019-0291-9. Epub 2019 May 27. PubMed PMID: 31133756; NIHMSID:NIHMS1527246.
• *Li Y, *Muffat J, *Javed AO, *Keys HR, Lungjangwa T, Bosch I, Khan M, Virgilio MC, Gehrke L, Sabatini DM, Jaenisch R (2019) Genome-wide CRISPR screen for Zika virus resistance in human neural cells. PNAS . 2019 Apr 24. doi: 10.1073/pnas.1900867116
  *equal contribution
  
• Kory N, Wyant GA, Prakash G, Uit de Bos J, Bottanelli F, Pacold ME, Chan SH, Lweis CA, Wang T, Keys HR, Guo YE, Sabatini DM (2018) SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. Science 362(6416). 2018 Nov 16. doi: 10.1126/science.aat9528
• Kanarek N, Keys HR, Cantor JR, Lewis CA, Chan SH, Kunchok T, Abu-Remaileh M, Freinkman E, Schweitzer LD, Sabatini DM (2018) Histidine catabolism is a major determinant of methotrexate sensitivity. Nature 559:632-636. 2018 July 11. doi: 10.1038/s41586-018-0316-7

Photo Credit: Conor Gearin


Heather Keys, Ph.D.

Director

Adina Kirkland

Technical Assistant I

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Alumni

Stephanie Esonwune, Strand Therapeutics
Olena Fedoniuk, Tokyo Institute of Technology Technical Support Staff and GLOBIS MBA student
Mehreen Khan, Alnylam Pharmaceuticals
Maria Virgilio, University of Michigan PhD Program
Keya Viswanathan


Former and current Masters Students

Nicole Eischer, IMC University of Applied Sciences Krems
Manuel Mastel, Heidelberg University

Materials

Here you can find basic protocols for screening and related experiments. More coming!

Any questions? Contact us

Protocols

Join Us

We are looking for motivated people to work with us.

If you are a motivated Masters student searching for an exciting internship experience, contact us!

Contact Us

Please contact Heather Keys, Ph.D. by email with all questions.

Elements

i = 0;

while (!deck.isInOrder()) {
    print 'Iteration ' + i;
    deck.shuffle();
    i++;
}

print 'It took ' + i + ' iterations to sort the deck.';