Model-guided design of ligand-regulated RNAi for programmable control of gene expression

Progress in constructing biological networks will rely on the development of more advanced components that can be predictably modified to yield optimal system performance. We have engineered an RNA-based platform, which we call an shRNA switch, that provides for integrated ligand control of RNA interference (RNAi) by modular coupling of an aptamer, competing strand, and small hairpin (sh) RNA stem into a single component that links ligand concentration and target gene expression levels. A combined experimental and mathematical modelling approach identified multiple tuning strategies and moves towards a predictable framework for the forward design of shRNA switches. The utility of our platform is highlighted by the demonstration of fine-tuning, multi-input control, and model-guided design of shRNA switches with an optimized dynamic range. Thus, shRNA switches can serve as an advanced component for the construction of complex biological systems and offer a controlled means of activating RNAi in disease therapeutics

Synthetic control of a fitness tradeoff in yeast nitrogen metabolism

Background: Microbial communities are involved in many processes relevant to industrial and medical biotechnology, such as the formation of biofilms, lignocellulosic degradation, and hydrogen production. The manipulation of synthetic and natural microbial communities and their underlying ecological parameters, such as fitness, evolvability, and variation, is an increasingly important area of research for synthetic biology. Results: Here, we explored how synthetic control of an endogenous circuit can be used to regulate a tradeoff between fitness in resource abundant and resource limited environments in a population of Saccharomyces cerevisiae. We found that noise in the expression of a key enzyme in ammonia assimilation, Gdh1p, mediated a tradeoff between growth in low nitrogen environments and stress resistance in high ammonia environments. We implemented synthetic control of an endogenous Gdh1p regulatory network to construct an engineered strain in which the fitness of the population was tunable in response to an exogenously-added small molecule across a range of ammonia environments. Conclusion: The ability to tune fitness and biological tradeoffs will be important components of future efforts to engineer microbial communities

Electrodynamics of Media

Contains reports on two research projects.Joint Services Electronics Programs (U.S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-0300U.S. Air Force Cambridge Research Laboratories Contract F19628-70-C -006

A Blow-Up Criterion for Classical Solutions to the Compressible Navier-Stokes Equations

In this paper, we obtain a blow up criterion for classical solutions to the 3-D compressible Naiver-Stokes equations just in terms of the gradient of the velocity, similar to the Beal-Kato-Majda criterion for the ideal incompressible flow. In addition, initial vacuum is allowed in our case.Comment: 25 page

Electrodynamics of Media

Contains reports on two research projects.Joint Services Electronics Programs (U.S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-0300U.S. Air Force Cambridge Research Laboratories Contract Fl9628-70-C-0064M. I. T. Sloan Fund for Basic Research (Grant 616

Diffusion MRI in early cancer therapeutic response assessment

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136261/1/nbm3458_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136261/2/nbm3458.pd

Electrodynamics of Media

Contains research objectives, summary of research and reports on one research project.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-0300U.S. Air Force Cambridge Research Laboratories Contract F19628-70-C-0064M.I.T. Sloan Fund for Basic Research(Grant 616)M.I.T. Lincoln Laboratory Purchase Order A-627