Proteins form the core arsenal of life, in signaling how living organisms behave, grow, and interact with their environment. To accomplish this range of biological functions, proteins have evolved remarkable attributes to interact specifically with other proteins, or with DNA. Recent discoveries have shown that certain conserved protein sequences have evolved the ability to "walk" along DNA in search of their target sites to enable this site-specific activity. The extraordinary speed and precision with which proteins accomplish this task remains a mystery, one that could have many benefits for engineering if the molecular precision of protein-DNA interactions could be reproduced in nanoscale synthetic systems. The research team will synthesize and characterize novel nanoscale materials that will behave like natural proteins in their ability to "walk" along DNA. This work could enable better understanding of how to design enzymes for bio-energy applications, antibodies for biological nanosensors, and protein-DNA interactions that drive all underlying cell processes. As a core component of the proposed research, the primary investigator will collaborate with Society for the Advancement of Chicanos and Native Americans in Science program at UC Berkeley to recruit two undergraduate students representing minority communities to the primary investigator's lab.
Brownian 1D diffusion of proteins along DNA enables protein-mediated cellular processes to occur on biologically-relevant timescales. Recent discoveries in protein biophysics have identified conserved sequences to facilitate 1-dimensional Brownian motion along DNA to expedite the target search process to a biologically-relevant timescale. Synthetic nanostructures have not been well-explored as bio-mimetic tools. Now that the "blueprints" for 1-dimensional Brownian diffusion are less elusive, the investigators propose an orthogonal study to apply these blueprints from biophysics to bioengineering. Here, the investigators seek to exploit these evolved features of site-specific proteins' 1-dimensional diffusion along DNA to build synthetic peptoid-based molecular machines. To-date, the study of synthetic motors has relied on the input of external sources of energy (chemical, photonic, etc). The investigators seek to exploit random (Brownian) mobility as a tool to build molecular translocators from synthetic bio-mimetic structures. Ultimately, the prediction is that the synthetic "Brownian machines" might carry molecular cargo, of potential applicability to fundamental and applied molecular and cellular research alike. This project combines high- resolution single-molecule fluorescence microscopy with robotic peptoid synthesis to develop a new class of synthetic materials capable of exploiting electrostatics for synthetic molecular machines. This work could be akin to the proof-of-principle exploratory research in scaffold-and-staple DNA-assembly that led to the field of DNA Origami. As a member of the underrepresented scientist community, the PI is both a strong supporter, and active leader in organizations supporting underrepresented scientists. This research effort will be integrated with the UC Berkeley Latino/a American Graduate Students in Engineering and Science program at Berkeley, and the Society for the Advancement of Chicanos and Native Americans. Prof. Landry will also organize and host the first nanobiosciences conference in Cuba, in collaboration with Prof. Dionisio Zaldivar Silva, Dean of the Faculty of Chemistry at the University of Havana Cuba. This NanoMEDD conference in Havana will be held using extramural funding that has already been secured.
