Life at the molecular level

Life is a complex phenomenon involving a vast number of specific and purposeful biochemical and biophysical processes. Every cell contains billions of components, performing very specific roles, which come together in a dazzling array of molecular pathways that describe phenomena at the cellular, tissue, organ, and ultimately the organism level.

A major challenge is understanding the mechanisms of the multifarious molecular machinery that come together to guide the cellular processes, and how the molecular chemical and physical properties of these affect the multi-scale mechanisms. How do signals from different processes determine if a cell stagnates, migrates, or proliferates? What processes allow communication of these choices to higher level organization (e.g. cell to tissue level translation of molecular decisions)? The signal to noise ratio is extremely poor (i.e. millions of simultaneous signals), and not consistent, yet molecular processes are robust and cyclically occur with high fidelity (e.g. DNA replication).

The answers to these questions require intimate knowledge of the individual molecules involved in these stochastic processes. The scientific community’s progress in obtaining this knowledge is deeply intrenched in single-molecule (bio)physics research.

It takes two to tango: protein-DNA interactions

Survival and propagation of cells rely crucially on interactions between DNA and proteins. A critical step is the interaction between proteins and specific DNA regions. Searching for and binding specific sites requires enormous speed and precision. How can a protein find its site on a long DNA molecule among millions of decoy sites?

We study different model proteins to elucidate the search mechanism involved in proteins identifying and binding specific DNA segments. This project employs novel combinations of single-molecule fluorescence imaging, magnetic tweezers, atomic force microscopy, and computational modeling to discover how the biophysical interactions involved in protein-DNA interactions contribute to the search process.

Toto, I’ve a feeling we’re not in Kansas anymore: protein self-assembly

Proteins are involved in nearly all cellular functions, and protein complexes must be in specific locations at specific times for a cell to function properly. Spatial or temporal deviations/disruption of this arrangement may lead to malfunction and disease, and ultimately to cell death. Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, are linked with specific proteins that self-assemble, due to an as of yet unknown cause, and cause disruptions in the normal cellular functions involving these proteins.

We study the disease-linked proteins to characterize the self-assembly process, identify the factors which affect the process, and to determine the initial steps of the process. The project employs novel combinations of time-resolved fluorescence imaging, atomic force microscopy, and computational modeling.