Project Overviews

  • 1. Chemical Interference

    "Our team generates and discovers small molecules that interfere with key biological processes to better understand their mechanism of action." 

    This project draws from different areas such as organic synthesis, organometallic chemistry, or natural products chemistry, and combines biological and predictive computational approaches.

    • Natural product libraries (Gademann)
    • Metallation to expand chemical diversity of scaffolds (Dyson)
    • Virtual screening and compound generation (Reymond)
    • Cyclic peptides (Heinis)
    • Platforms for multitopic interference (Lacour)
    • Diversity oriented synthesis (Waser)
    • Unnatural nucleic acids (PNA) (Winssinger)
    • Natural products and heterocycles (Zhu)

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    project 1 details

  • 2. System Level Chemical Interference

    "We establish generic protocols to discover novel, potent, cell-permeable small molecule inhibitors specific for defined targets using a yeast model."

    By ingeniously exploiting state-of-the-art high throughput screening resources, this project supports breakthroughs in molecular biology.

    • Target of Rapamycin (TOR) kinase inhibitors (Loewith)
    • Histidine kinase inhibitors (Loewith)
    • Ceramide synthase inhibitors (Riezman)
    • ERAD and Cdc48 inhibitors (Gotta)
    • Sphingolipid metabolism inhibitors (Riezman
  • 3. Membrane Localization and Endocytosis

    To avoid adaptive responses associated with genetic manipulations, this project identifies compounds that interfere with endosomal functions on a real-time scale.

    We use state-of-the-art high throughput screening resources to identify relevant small inhibitors of protein and lipid trafficking/sorting in mammalian cells. We also develop innovative strategies to probe both aqueous and membrane environments.

    project 3 details

    PERSPECTIVES / HIGHLIGHTS

  • 4. Signal Transduction

    "We monitor and manipulate kinases in living cells with high temporal and spatial resolution."

    Aurora-A and Plk4 are two kinases that play critical roles in human cells during mitosis and centrosome duplication, respectively. The objective of this project is to develop and implement new approaches to investigate and interfere with the activity of such kinases with high spatial and temporal resolution.

  • 5. Notch Signaling

    "We devise high throughput screening systems to identify novel small molecules and druggable targets which interfere with Notch signaling in cancer."

    This project uses complementary chemical approaches to study Notch signaling in physiological and pathological situations. We also visualize and control Notch signaling in living cells.

    • Specific anti-tumor agents for Notch-mediated tumorigenic activity (Radtke
    • Validation of positive hits during model system development (González-Gaitán
    • High throughput cell culture systems to assess Notch signaling and targets (Radtke and Zhu)
    • Identifying peptide-based inhibitors of Notch interactions (HeinisRadtke)
    • Development of Notch biosensors (González-Gaitán
  • 6. Biophysics of Cell Division

    Using physics and chemical biology to understand asymmetric division in model organisms.

    This project studies asymmetric cell division, a prominent developmental event which is central for the self-renewal of stem cells. Asymmetric division is the basis of tissue homeostasis and, when faulty, can lead to pathological behaviour such as that observed in cancer stem cells.

  • 7. Cellular Uptake and Membranes

    "It is essential to find conceptually new ways to get into cells."

    This project focuses on conceptually innovative approaches to new transport systems for applications to cellular uptake and new fluorophores for applications as membrane probes. 

ACCESS

An Academic Chemical Screening Platform for Switzerland

ACCESS provides the scientific community in Switzerland with chemical diversity screening facilities and know-how in chemical genetics.
It allows the Swiss academic community to profit from the enormous possibilities of chemical biology. ACCESS will also permit Switzerland to become part of larger European efforts in the field of chemical genetics.  

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