Employ single-molecule analysis of eukaryotic replication fork dynamics to study the mechanisms of DNA replication inhibitors.

Identify antiviral drug candidates (for viruses such as influenza, HIV, and Dengue) through a single-particle approach that allows high-throughput assaying of viral membrane fusion.

Multiplex (that is, lab-on-a-chip) single-molecule imaging processes.

• Dr. van Oijen’s cutting-edge imaging analysis of biological processes at the single-molecule level is leading to new breakthroughs in understanding molecular mechanisms of biological processes.
   
• His studies on DNA replication are revealing new findings about the intricate protein interplay that produces coupling of leading and lagging strand synthesis.
   
• His research on viral fusion mechanisms may yield important mechanistic insights for a variety of viruses that depend upon fusion as a prerequisite for internalization.
   

• Single-molecule image analysis with advanced fluorescence microscopy.
• Analysis of DNA replication forks.
• Reconstitution of viral fusion with purified components.

Dr. van Oijen applied his biophysical training to analyses of biological processes, such as DNA replication. His studies on the prokaryotic and eukaryotic replication forks led directly to important insights about how the DNA replication machinery coordinates leading and lagging strand synthesis. He made these breakthroughs by using real-time measurements at the single-molecule level, a recently-developed, and increasingly popular, technology that uses sophisticated and highly sensitive fluorescence microscopy. His research on the communication among replication enzymes as well as replication loops was published in two recent articles appearing in Nature.

Dr. van Oijen also studied the DNA repair mechanisms that remove DNA lesions. He recently expanded the applications of his single-molecule imaging methodology to the process of viral fusion with cell surface membranes.
 

Fluorescence microscopy image of individual influenza particles fusing with a planar target membrane. Different colors correspond to the fluorophores that are embedded in the particles to track various fusion intermediates. The yellow diffuse clouds represent particles after fusing, while the discrete pinpoints are virus particles docked to the surface that have not fused yet.
 

Biological Mechanisms and Pathways

• DNA helicase •
• DNA Polymerase •
• DNA primase •
• DNA Replication •
• DNA Replication •
• Viral fusion
•  

Disease Mechanisms

• Dengue Virus •
• Flu •
• HIV •
• Influenza •
• Membrane-enveloped viruses
•  

Infectious Disease

• Dengue Virus •
• Dengue Virus •
• HIV •
• Influenza •
• Influenza
•  

Research Tools and Instrumentation

• Lab-On-A-Chip •
• Microfluidics •
• Multiplexing •
• Single molecule imaging
•