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 ::  New single-molecule imaging techniques and assays for biomedical research

 
We develop and use state-of-the-art single-molecule fluorescence imaging techniques, such as multi-color single-molecule localization microscopy, single-molecule FRET and single-molecule tracking, to study specific molecular features and mechanisms of biological systems.  Single-molecule probing methods provide unique information that cannot be obtained with conventional ensemble techniques due to averaging.  These cutting-edge techniques offer new probing capabilities to monitor dynamics of individual proteins and complexes in real time, and image molecules in cells with a resolution of several nanometers. These methods are conceptually groundbreaking and extremely promising in providing a plethora of new information and shedding light on major biological questions.
 

 :: Genomic metabolism, maintenance of genomic integrity and DNA damage response

 
DNA is subjected to various genotoxic stresses from regular cellular DNA metabolism processes, such as replication and transcription, or from external factors, such as radiation and reactive oxygen species. The cell employs a vast array of enzymes and proteins to survey, detect and maintain the integrity of the genome. The DNA damage response (DDR) and repair pathways play a critical role in maintaining genomic stability and preventing cancer. Disruption of these pathways by mutations in genomic integrity proteins increase cancer incidence in patients, indicating that these proteins are essential for prevention of tumorigenesis. We use single-molecule approaches to study the mechanisms of key processes in Genomic metabolism.
 

:: Molecular architecture of the cardiac connexome

 

Cardiac myocytes are highly differentiated, specialized, and compartmentalized cells. Proteins organize in defined microdomains. Slight changes in the position of a protein within its domain can bring about a major disruption in function. Cardiac cells form highly organized specialized cellular junctions which couple cellular communication, signal and force transduction and electrical activity. We use single-molecule microscopy tools to map molecular interactions and architecture of cellular junctions in cardiac cells. 

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