The recently completed human genome sequence is yielding a plethora of potential new targets for intervention by novel therapeutic agents in a variety of diseases. These therapeutic agents will be developed against targets identified through a better understanding of the function of the genes and proteins involved in disease initiation and progression. In order to effectively and competitively exploit the genome data, an industrialized multidisciplinary and process-driven approach was instituted in the Functional Genomics Department for drug target identification and validation. This allows the generation of a multidimensional profile of potential and promising targets for drug development.

Functional Genomics comprises the following units:
 

Proteome sciences
This unit is dedicated to the emerging field of proteomics. Its mission is to solve a researcher's biological question by identifying and characterizing proteins of interest, and understanding their interactions with other proteins.  As proteomics offers new insights into complex biological questions, it has applications in a wide range of areas in biomedical research and drug discovery. The technologies involved in proteomics today are many and varied, and generally address two technical issues: the separation of proteins, and their identification and characterization. One widely used paradigm combines two-dimensional gel electrophoresis with mass spectrometry.

Nucleic acid sciences
This unit focuses on high-throughput synthesis and screening of oligonucleotide derivatives to help understand nucleic acid-based mechanisms in the cell, and application thereof to help understand gene function. This unit also develops methods for improving use of oligonucleotides in animal models of disease by tailoring their chemical composition to the in vivo environment and optimizing reagents for delivery to the target tissue.

Molecular genetics
The main technology platform of this unit centers on the rapid systematic evaluation of gene function in cell based assays.  The foundations for this work are 1) a comprehensive set of reagents (full-length cDNAs and siRNAs)  that allow overexpression or "knockdown" of the majority of human genes, and 2) automation and miniaturization of gene transfer and phenotypic screening. Together, these tools allow us to begin determining each genes contribution to disease-relevant signal transduction pathways and cell based phenotypes. 

Drosophila genetics
This unit utilizes the fruitfly, Drosophila melanogaster, as a genetic model system for the study of disease-related pathways and for the identification of new drug targets. This is feasible because functional conservation of genes, pathways and processes between fruit flies and humans allows the results obtained using this genetically tractable model organism to be applied to humans.

Life science informatics
This unit is the central computational biology group within the Novartis Institutes for BioMedical Research. It focuses on the discovery of novel target genes for medical therapies or potential biomarkers utilizing in-silico methodologies. Key projects include the discovery of novel members of drugable protein families, the computation of an in-house version of the human transcriptome utilizing all available public and proprietary sequence information, the development of an integrated database for microarray gene expression data, which allows for database-wide analysis strategies, computation of a genome-wide RNAi collection, and in-silico prediction of sequences having an optimal efficiency as suppressors. The Life Science Informatics group works in close collaboration with computational biologists in the individual disease areas and the research informatics group (IK@N).

Functional Genomics is headed by Dalia Cohen and is located in Basel, Switzerland and Cambridge, USA.

Hall J. Unraveling the general properties of siRNAs: strength in numbers and lessons from the past. Nature Reviews Genetics  5(7), 552-227 (2004).

Dorn G, Patel S, Wotherspoon G, Hemmings-Mieszczak M, Barclay J, Natt F, Martin P, Bevan S, Fox A, Ganju P, Wishart W, Hall J. siRNA relieves chronic neuropathic pain. Nucleic Acids Research, 32, e49 (2004).

Towbin H, Bair KW, DeCaprio JA, Eck MJ, Kim S, Kinder FR, Morollo A, Mueller DR, Schindler P, Song HK, van Oostrum J, Versace RW, Voshol H, Wood J, Zabludoff S, Phillips PE. Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors. J Biol Chem. 278(52):52964-71 (2003, Dec 26).

Wang S, Yan-Neale Y, Fischer D, Cai R, Zhu J, Burfeind P, Hampton G, and Cohen D.  Histone deacetylase 1 represses the small GTPase RhoB expression in human nonsmall lung carcinoma cell line.  Oncogene 22, 6204-6213 (2003).

Iourgenko V, Zhang W, Mickanin C, Daly I, Jiang C, Hexham J, Orth A, Miraglia L, Meltzer J, Garza D, Chirn G, McWhinnie E, Cohen D, Skelton J, Terry R, Yu Y, Bodian D, Buxton F, Zhu J, Song C, and Labow M.  Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cells.  PNAS 100 (21): 12147-12152 (2003).