Join Us! We are looking for a few talented and energetic researchers to join our team. If you're interested in any of these project areas and have some ideas you'd like to put to the test, contact Professor March at the following email address: jcm224@cornell.edu. If you're sending blanket emails to nearly everyone in the academic universe, please don't reply. |
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Welcome
to the Metabolic and Signal Engineering Lab's of John C. March. We are
located in the Department of Biological
and Environmental Engineering at Cornell
University. This web page is intended to tell you more about our research
in metabolic engineering and signal transduction control. Metabolic processes
are a constant, driving force behind natural selection. As organisms adjust
to their environment and compete for available resources, it is often
lightning-quick metabolic signal cascades that allow for rapid responses
to threatening conditions such as changing a carbon source when one becomes
scarce or secreting a carbohydrate in response to osmotic shock. Here
we attempt to understand the forces at work behind metabolism and harness
the power of signal transduction in the development of technological tools.
Some specific examples of projects areas we are interested in are below.
Adaptive gene silencing
Microorganisms have several mechanisms for sensing and responding to their environments. We want to learn more about these mechanisms (such as promoters, enhancers, and inhibitors), and incorporate them into biotechnological solutions to a wide variety of problems. By using tunable gene silencing via RNA interference (RNAi), short RNAs (sRNA), or micro RNA, we can study the dynamics of signaling cascades that are controlled by sensing mechanisms. From here we use cell signaling and tunable gene expression to correct and enhance target organisms so they can more effectively adapt to environments that we define.
High throughput pathway development
Highly toxic and/or stable compounds such as VX nerve gas or trichloroethylene require several steps and in some cases consortia of microorganisms to mineralize. These processes are complicated, challenging to repeat in a laboratory setting (where steady state kinetics often can't be emulated), and hence, very difficult to characterize, much less optimize. We are developing platforms to simultaneously screen several species of microorganism for their ability to convert recalcitrant compounds into benign and, where possible, value-added products. Using micro-electrical-mechanical (MEM) devices we will be able to finely control environments where several configurations of organisms and environmental parameters can be screened for their ability to convert wastes to products. The MEMs platform allows for much tighter control of the environmental space and greatly reduces the cost of performing several experiments simultaneously.
Reconfiguring probiotics as recombinant therapeutics
This research involves the development of modular expression cassettes that will re-configure target organisms for safe and effective therapeutic synthesis within a mammalian host. We are engineering enteric bacteria into effective in vivo cellular factories, responding to a specific molecular imbalance by synthesizing an appropriate corrective therapeutic. Cellular therapies share a need for accurate detection of target molecule levels, benign coexistence within the host, and a sufficient level of tunable gene expression.