Physics of Cellular Systems

   Research

       We study the role of free energy and geometry in cell biology. This includes how energy and geometry        physically limit biological processes, and how energy and geometry are used by cells to provide        improved performance.

                     Current Projects

       

Glycoprotein quality control cycle

Energy and kinetics for protein quality control
Newly-synthesized proteins must fold into a three-dimensional structure to become functional, a process that is often facilitated by chaperone proteins. Proteins can also misfold into an incorrect structure that is not functional. Misfolded proteins, and proteins that have yet to fold, can aggregate, causing problems and endangering cell health. Cells have protein 'quality control' to sort correctly folded proteins to their final functional destinations, and target misfolded proteins for degradation. Glycoprotein quality control is a cyclic process, driven by free energy and with many kinetic steps. This project studies how the energy use and kinetic features of glycoprotein quality control lead to improved protein production and limited accumulation of unfolded proteins with finite chaperone available to help proteins fold.

       

Mitochondrial network

Mitochondrial network dynamics and protein localization
Mitochondrial tubes form extended networks with branches and loops. These networks are dynamic, undergoing fission (tubes splitting apart), fusion (tubes merging together, both end-to-end and end-to-side), growth, and degradation. Proteins move through these networks, diffusing, binding and unbinding, reacting, and degrading. How do network dynamics control the spatial localization of proteins in the network? How does the impact of protein populations on network dynamics regulate the protein populations themselves? We seek the physical limits and controlling factors for protein localization in dynamic mitochondrial networks.

       

mRNA diffusing to
mitochondrial network

Nonequilibrium control of mRNA localization to organelles
Although mitochondria have their own DNA, many mitochondrial genes are encoded in nuclear DNA, translated into proteins by ribosomes in the cytosol, and imported into mitochondria. mRNA localization to mitochondria can play a role in regulating mitochondrial protein concentrations. A protein can begin import into a mitochondrion as a ribosome is still translating a protein, effectively tethering an mRNA to a mitochondrion. mRNA for some genes spend most of their time near mitochondria, some spend very little, while others significantly increase their mitochondrial localization as the volume of mitochondria in the cell increases. We explore how the combination of cell geometry and the nonequilibrium conditions of protein translation combine to determine mRNA localization to mitochondria. We also probe the stochastic effects of finite mRNA number and localization on protein concentration fluctuations between individual mitochondria.

       

Endoplasmic reticulum network

Biomolecular signaling dynamics under confinement
Biomolecular signaling and kinetics is often understood in the relatively large volumes of a whole cell or even a test tube. However, a lot of signaling inside cells occurs inside even smaller organellar compartments. We explore the unfolded protein response (UPR) inside the tubes and sheets of the endoplasmic reticulum (ER). The UPR signaling system activates under the stress of excess unfolded proteins, activating receptors in the ER membrane to form pairs and clusters. How is the behaviour of the UPR, inside the narrow spaces within ER tubes and sheets, affected by this confinement and by the network shape of the ER?

       

Cyclic kinetics

Nonequilibrium selection of organelles for degradation
Cell biology is driven and directed by the dissipative expenditure of free energy. Performance can be improved by using free energy to drive cyclic processes, such as the cycles for 'kinetic proofreading' that enable the high accuracy of DNA replication. Another cyclic process consuming free energy is the addition of proteins that label organlles for degradation. How does the selection of organelles for degradation improve with free energy expenditure, and trade off with other performance measures like speed?

                     Published research