Monday, December 15, 2014

The Art of Scientific Proposals

When I was taking HPS (History and Philosophy of Science) Tripos at the University of Cambridge last year, I remembered having a hard time debating with friends and supervisors what are the best way to ensure that the “right” science gets public funding while the “wrong” one doesn’t. In the end, we had to agree that even though not a perfect solution, the current paradigm of proposing research ideas to funding agencies is the best way we can practically do. Indeed, not every research project entitles the same amount of resources, and it is our job as scientists and engineers to justify our particular choice of research. I therefore really appreciate the opportunity in 20.109 to develop our own proposal after learning the many useful experimental skills.

It wasn’t easy though. Three of us came up with 15 different ideas in the beginning and we were pretty lost after lab 2 when we met and discussed our common interests – there wasn’t any significant overlap, and in fact, we weren’t even very clear what we were interested in carrying out. Phage biotemplating was pretty cool, and so is rewiring signal transduction pathways. Maybe we should apply the same technique to other model systems or other pathways? Say a bacterial/mammalian system that can sense broad-band EM wave instead of light, or a capacitor (and hence memory device) that is constructed by phage? Or more concretely, can we apply a new enzyme recently synthesized in T-cells to our intestinal stem cells, or apply optogenetics technology to engineer not only neurons but also inner hair cells around our cochlea?

Over the Thanksgiving break, we read more than 50 papers on the topics we were interested in, and to our great surprise and dismay, all of these ideas have been developed or are being actively investigated by labs around the world. But the good news is, we now realized that we are interested in and also good at quantitative modeling of biological systems (since we found pure biology articles extremely hard to read), and after Shannon’s and Agi’s insightful suggestions we were able to identify two different types of modeling which we can connect to create new possibilities. After reading extensive literature, we were inspired by the fact that there isn’t a commonly agreed way to classify such a common disease like colon cancer, and the fact that there are still new proteins being associated with the colon tumorigenesis Wnt pathway despite extensive studies for the past 30 years. That is when we decided to focus on the Wnt pathway (with cross-talking EGF, Notch, and BMP pathways) in intestinal stem cells as our research project.

The preparation for our proposal went much smoother after we identified the problem to work on and learned a few key modeling techniques to use. We can now appreciate the importance of having a well-defined set of questions to answer and goals to achieve, as well as a set of essential tools to use in order to make a convincing proposal. We realized that it is never a bad idea to talk to people from different backgrounds and brainstorm new ideas before focusing on specific areas of interest. Most importantly, we also realized that proposing new research ideas is an art as much as it is science such that there is nothing to fear about being creative. 

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