Our multidisciplinary approach
We are a diverse group of scientists with backgrounds in cell biology, biochemistry, biophysics, genomics, and computer science, united by a passion to uncover fundamental mechanisms in biology. We are committed to pursuing creative and innovative approaches and conducting experiments with the highest rigor. Fairness, respect, honesty, and mutual support are core values of our team.
Because we like to ask unconventional questions, we often must establish new techniques to study cellular processes. We exploit a broad panel of advanced microscopy techniques and combine them into correlative workflows to bridge the gap in resolution between molecular and cell biology. By combining genomics tools like Hi-C with multiplexed fluorescence hybridization and live-imaging approaches, we aim to understand the dynamic 3D organization of the genome. This multi-disciplinary approach has allowed us to discover novel biological phenomena for which molecular regulators have not yet been described.
To elucidate the molecular foundation of these previously undescribed phenomena, we perform image-based loss-of-function screening. Computer scientists in our laboratory have implemented CellCognition, a fully automated, live-cell microscopy platform to perform cell phenotype analysis by machine learning. New molecular regulators identified by image-based screening are systematically characterized in cells using state-of-the-art molecular techniques, including CRISPR/Cas9-based genome engineering, readouts using biosensors, chemically induced protein dimerization, and micro-manipulation using intracellular laser surgery.
Once we have determined the cellular functions of novel regulators, we aim to dissect the underlying molecular mechanisms. We characterize molecular properties using a variety of biochemical technologies, including systematic analysis of molecular interactions and posttranslational modifications by mass spectrometry.
We then use in vitro reconstitution with purified components to test hypotheses about molecular mechanisms. For example, biochemists in our team have established novel assays to study the mechanical properties of mitotic chromosomes using purified chromatin, DNA-coated beads, and recombinant proteins. We manipulate the components in this system using microfluidic chambers and magnetic force control and analyze biophysical properties using light- and atomic-force microscopy. Ultimately, our goal is to reconstitute molecular activities using synthetic components that mimic the functions of native cellular proteins.
The ability to pursue an idea that begins with a general description of cellular biological processes and results in a detailed understanding of mechanistic details of the molecular components requires a broad range of technologies. We are able to accomplish this because of the outstanding research infrastructure available at campus facilities, and our strong network of international collaboration partners. Researchers in our laboratory take the lead in developing hypotheses and establishing the experimental assays and approaches to address them, but they are extensively supported by our facility staff. This teamwork approach leverages our research beyond the boundaries of individual biological disciplines and allows us to accomplish ground-breaking science.
Technologies and model systems
The cutting-edge technologies provided by the scientific facilities at our campus offer an unmatched opportunity to focus entirely on biological questions, rather than troubleshooting technical details. At IMBA, we have free access to a variety of microscopes at the forefront of imaging through the BioOptics and Electron Microscopy facilities. This large collection of scanning- and spinning disc confocal microscopes, automated screening microscopes, laser microsurgery, super-resolution fluorescence, and electron microscopes enables us to approach scientific questions from multiple angles.
Our biochemical work is supported by the Protein Chemistry, Protein Technology, and Metabolomics facilities, and chromosome conformation capture experiments are carried out in collaboration with the Next Generation Sequencing facility. Genome engineering and molecular biology services are further supported by Protein Technology and Molecular Biology facilities.