Metabolic and Signal Engineering

Welcome to the Metabolic and Signal Engineering Labs 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 and signal engineering. Signaling is how cells communicate with one another and with the world around them. That world can be a single villus in the GI tract or a parcel of sea water in the Atlantic. Information about how many, how long, where, what type and what to do next is constantly streaming in and out of cells (both prokaryotic and eukaryotic) in the form of proteins, small molecules, ionic species and chemical gradients. Making sense of all this signaling is the daily work of the cell. Making sense (and use) of what the cell does with it is the daily work of our lab. Below are some examples of projects we are working on. To learn more, feel free to contact Professor March at jcm224 at cornell dot edu.
Image of mouse intestinal cells after colonization with V. cholerae, pre-treated with commensal bacteria (L) or commensal bacteria expressing a V. cholerae quorum signal (R). Red staining indicates the presence of cholera toxin.	NEWS Chris Aurand and Matt Russell publish "Synthetic signaling networks for therapeutic applications" in Current Opinion in Biotechnology! Jay Sung and Jiajie Yu's paper on in vitro intestinal models is published in Lab on a Chip (Link). Nice work!! Houchun Liu joins the lab. Welcome Houchun!! Faping Duan's paper gets mentioned in Science Signaling as an editor's choice: http://stke.sciencemag.org/cgi/content/abstract/sigtrans;3/128/ec193 ...and again in ASM's Microbe: http://www.microbemagazine.org/index.php/10-2010-current-topics/2840-minitopics Way to go, Faping!! March gets an NIH New Innovator award... http://nihroadmap.nih.gov/newinnovator/recipients10.asp Matt Russell's paper, "Bootstrap estimation of confidence intervals on mutation rate ratios." has been accepted to Enviromental and Molecular Mutagenesis. Congrats, Matt!!
Reconfiguring probiotics as recombinant therapeutics	Interspecies signaling research platforms	Adaptive gene silencing
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.	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. Taking advantage of the Cornell Nanofabrication Facility and working with collaborators with expertise in material science we are developing several microfluidic reactor formats for studying how species communicate with one another and with their environments. Examples include microfluidic chemostats for studying bacterial signaling in series and "gut tube reactors" for mimicking the upper GI tract. These reactors are being specifically designed to extract information that is normally not possible in traditional cell culture formats. In the long term we are looking to improve in vitro models to the point that they are more accurate and reliable than competing in vivo models for understanding signaling interactions.	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.