CB 399: Nanocourse: Functional Genomics and Screening Winter 2015

Nanocourse: Functional Genomics and Screening

Nanocourse Director: Dr. Fred Winston
Curriculum Fellow: Emily Gleason, Emily_Gleason@hms.harvard.edu 


  • Dr. Steve Elledge, Professor of Genetics, Harvard Medical School
  • Dr. Norbert Perrimon, Professor of Genetics, Harvard Medical School
  • Dr. Stephanie Mohr, Director of the Drosophila RNAi Screening Center, Co-Director of the Genome Engineering Production Group, and Coordinator of the DF/HCC Collaborative RNAi Core, Harvard Medical School
  • Dr. Jen Smith, Assistant Director of the ICCB-Longwood Screening Facility, Harvard Medical School
  • Dr. Caroline Shamu, Director ICCB-Longwood Screening Facility, Harvard Medical School

Cultured cells provide a powerful system for studying fundamental problems in topics such as signal transduction, cell differentiation and physiology. Several approaches can be used to interrogate gene function at genome-wide scale in cultured cells, including established techniques such as RNA interference (RNAi) and over-expression, and newer techniques such as the use of miRNA mimics and inhibitors. In addition, the new genome engineering technologies, including the CRISPR/Cas system, can be used to modify cell lines (e.g. for assay development), to screen at high-throughput, and to follow up on screen candidates. This nanocourse will introduce the types of cell-based assays that can be performed at high-throughput scale; the types of reagents and genome-scale reagent libraries available to interrogate protein-coding and non-coding genes; and how bioinformatics and experimental approaches are used to analyze, verify and validate screen data. We will discuss advantages and caveats to the approaches presented, as well as discuss how RNAi and the CRIPSR/Cas system can be used in a complementary fashion to interrogate specific cell functions and generate high-confidence results.

Schedule: (First session is open to public, second is for registered students only) *NOTE DATE CHANGE FOR SECOND SESSION*

First Session: Wednesday, January 28th, 1 – 4:30 PM 
Location: TMEC, Rm 227
Second Session: Wednesday, February 11th*, 1 – 3:30 PM
Location: TMEC, Rm 448


Registered students should read the following papers (pdfs available below, you must be logged in to access them):

1. (siRNA) Adamson B, Smogorzewska A, Sigoillot FD, King RW, Elledge SJ (2012). A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response. Nat Cell Biol 14(3):318-28. PMID: 22344029

2. (CRISPR/Cas9) Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation.Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, Guimaraes C, Panning B, Ploegh HL, Bassik MC, Qi LS, Kampmann M, Weissman JS.Cell. 2014 Oct 23;159(3):647-61. doi: 10.1016/j.cell.2014.09.029. Epub 2014 Oct 9.PMID: 25307932

3. (in vivo RNAi) A regulatory network of Drosophila germline stem cell self-renewal. Yan D, Neumüller RA, Buckner M, Ayers K, Li H, Hu Y, Yang-Zhou D, Pan L, Wang X, Kelley C, Vinayagam A, Binari R, Randklev S, Perkins LA, Xie T, Cooley L, Perrimon N. Dev Cell. 2014 Feb 24;28(4):459-73. doi: 10.1016/j.devcel.2014.01.020. PMID: 24576427

Students should then write one discussion question for each paper based on information in the paper and the topics discussed during the first session of the course. The questions are due at 5pm on Sunday, February 8th. Students must then choose one of their questions and prepare to lead a brief (5-10 minute) discussion on that question during the second session. Depending on time constraints and the class size, not all students may be called on to lead the discussion. The students and lecturers will receive a copy of all of the submitted questions prior to the second session and students should be prepared to discuss all questions.

Additional Background Reading:

1. Mohr SE, Smith JA, Shamu CE, Neumuller RA, Perrimon N. (2014). RNAi screening comes of age: improved techniques and complementary approaches. Nat Reviews. Sept (15):591-600.

2. Wang T, Wei JJ, Sabatini DM, Lander ES. Genetic screens in human cells using the CRISPR-Cas9 system.Science. 2014 Jan 3;343(6166):80-4. doi: 10.1126/science.1246981. Epub 2013 Dec 12.PMID: 24336569

DROP DEADLINE: Wednesday, January 21, 2015