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Seeds

Structural and biophysical characterization of flagellar bend formation

Eukaryotic cilia and flagella are a marvel of evolutionary engineering. In this highly conserved organelle, thousands of motor proteins coordinate to generate a large scale, high frequency (~50Hz) beating motion that enables cells to move or propel fluid. Our goal is to characterize how constraints built into the structure of the flagella, such as an elastic nexin link that binds neighboring microtubules, effect its function. Using genetics we will systematically remove individual building blocks (proteins) of the flagella, identify these components using electron microscopy, and relate this data to the overall material properties of the flagella. Our systematic deconstruction of this complex hierarchical biological nanomachine will provide valuable lessons  for the design of novel biomimetic materials.

Dynamics of Transcription Factor Release from DNA

Transcription factors are proteins that control the development and environmental responses of all cells. Transcription factors function by recognizing and forming stable interactions with a nucleotide sequence located at a defined, single location on a long duplex DNA polymer. In this project, we will investigate the underlying physics that govern the dynamic interactions of transcription factor proteins with DNA, processes which are fundamental to the regulation of gene expression in all organisms. Using singlemolecule fluorescence microscopy techniques developed in the lab, we will make precise quantitative measurements of the lifetime distributions for complexes between individual transcription factor molecules and single linear DNA molecules that are immobilized by attachment of one end to a surface.

Intracellular hydrogelation resulting from self-assembly of small molecules

Recent studies reveal that the self-assembly of nanofibers within gels, like the formation of cellular nanostructures (e.g., actin filaments, microtubules, and viral capsids), follows a nucleation and growth mechanism. This common feature leads to an intriguing and poorly explored question: How does a cell respond to the intracellular hydrogelation resulting from the self-assembly of small organic molecules? To answer this question, we will form a hydrogel of small molecules inside cells. The conventional routes (e.g., a change of temperature, pH, or ionic strength) for making a supramolecular hydrogel, however, disrupt cellular processes and prevent precise evaluation of intracellular selfassembly. The goal of this seed project is to develop a new method in which an enzyme catalytically converts a precursor to a hydrogelator and triggers molecular self-assembly and hydrogelation