Functional Neurogenomics


Welcome to the website of the Division of Functional Neurogenomics (Gilbert Group) at the Institute of Medical Biotechnology. Our research focuses on the development and application of novel approaches in cell-based high-throughput screening for studying neuronal mechanisms in homeostasis, development and disease. We engineer instruments and computational tools for automated high-content fluorescence imaging and data analysis. We design innovative in vitro models and we apply our technologies for investigating neurotransmission, -pharmacology and –toxicity using small molecule and RNAi libraries.

Neurotransmission in the central nervous system

We are interested in chloride channels, in particular glycine and gamma-aminobutyric acid receptors (GlyR, GABAAR) and their role in homeostasis, development and disease. Glycine and GABAA receptors mediate inhibitory neurotransmission in the central nervous system (CNS). Dysfunction has been linked with neurological, neurodegenerative and psychiatric disease and is also associated with cancer. We use high-throughput and high-content screening technologies to identify genes involved in GlyR and GABAAR expression control as well as novel compounds active at those receptors. Chemical modulators of receptor function and expression can serve as leads for therapeutic development and as pharmacological tools for basic research, in research on synapse formation, homeostasis and plasticity as well as in developmental cell biology.

High-throughput technology development

We develop technologies for high-throughput screening in cultured cells and computational methods to analyze phenotypic data sets, including the development of miniaturized assay formats, phenotyping by single cell-based functional analysis of ion channels and new approaches for massively parallelized microscopy.

HTS Example: Identification of drug-target interactions

HTS Cancer

Literature

  • Gilbert DF, Jaedicke A, Boutros M. Hochdurchsatz-Screening von Wirkstoff- und Signalweg-Interaktionen. Laborwelt, Nr. 1 / 2010 – 11. Jahrgang
  • Gilbert DF, Islam R, Lynagh T, Lynch JW, Webb TI. High Throughput Techniques for Discovering New Glycine Receptor Modulators and their Binding Sites. Front Mol Neurosci. 2009;2:17. Epub 2009 Oct 30. PubMed PMID: 19949449; PubMed Central PMCID: PMC2782790.
  • Bartz F, Kern L, Erz D, Zhu M, Gilbert D, Meinhof T, Wirkner U, Erfle H, Muckenthaler M, Pepperkok R, Runz H. Identification of cholesterol-regulating genes by targeted RNAi screening. Cell Metab. 2009 Jul;10(1):63-75. PubMed PMID: 19583955.
  • Gilbert DF, Wilson JC, Nink V, Lynch JW, Osborne GW. Multiplexed labeling of viable cells for high-throughput analysis of glycine receptor function using flow cytometry. Cytometry A. 2009 May;75(5):440-9. PubMed PMID: 19184990.
  • Gilbert D, Esmaeili A, Lynch JW. Optimizing the expression of recombinant alphabetagamma GABAA receptors in HEK293 cells for high-throughput screening. J Biomol Screen. 2009 Jan;14(1):86-91. PubMed PMID: 19171924.
  • Kruger W, Gilbert D, Hawthorne R, Hryciw DH, Frings S, Poronnik P, Lynch JW. A yellow fluorescent protein-based assay for high-throughput screening of glycine and GABAA receptor chloride channels. Neurosci Lett. 2005 Jun 3;380(3):340-5. Epub 2005 Feb 23. PubMed PMID: 15862914.