The Unknown Assumptions behind an MCB Mindset

Written by Billal Ahmed (PEACE Advisor)

To be honest learning a shit ton of MCB is more about thinking in a certain mindset than knowing a set of material, though there is obviously important material to be understood. I gained a lot of my MCB perspective/insight from a) taking MCB C100A and b) working in an MCB lab. The former provided me with a solid thermodynamic and kinetic framework with which to understand biology, and the latter has trained me to ask certain kinds of questions and view systems in a particular manner.One of the most important part of MCB is understanding molecular pathways that involve multiple steps: for example, Substrate A being converted to Substrate B being converted to substrate C, or something along those lines.

In this hypothetical system there are a few things to note:

a) This is merely a chemical reaction in which A–>B–>C. Using this you can apply knowledge of chemical kinetics and thermodynamics to make quantitative and qualitative statements about the quantities and rates of change of these species.

b) Something that affects one part of the pathway probably affects another part of the pathway. For example, let’s say we introduce an enzyme into this system that breaks down A. Assuming the step A–>B is not zero order, because the concentration of A will go down, the overall step will slow down. This will cause B to appear less quickly, which will in turn affect the rate of B–>C. This concept isn’t particularly difficult to understand if you have a solid chem background, but it’s important because MCB people often want to study “inhibition” of a pathway, and inhibition can come at many steps in a chain.

c) In molecular biology, things tend to be a bit on the qualitative side, so when discussing species that inhibit or activate a pathway, people tend to use a binary notation where a certain species either “activates” or “inhibits” another species. For example, in my research I’m studying a Viral Protein (let’s call it A) that activates transcription of a host immune response molecule. This is done by the following pathway: A (inhibits) B (activates) C (inhibits) D. In other words, protein A inhibits the fuctionality of species B, which activates the functionality of species C, which inhibits the production of species D. Note that Protein A inhibits the activator of an inhibitor, which leads to activation (in other words, the inhibitor of an an inhibitor is an activator). You can also think of it as a system where inhibitory steps are negative signs, activatory steps are positive signs, and you literally multiply signs together to discern the net effect. In this case, a negative times a positive times a negative yields a positive, so in this case A will activate D.

Another important aspect of MCB is knowing your biomolecules, their properties, and what sorts of assays you can perform to analyze them. This requires you to know structure/function and all of the techniques you could use. I’m guessing you’ll be getting this out of your syn bio course, because this is fairly easy to teach in a classroom setting. A simple example of this would be understanding how the Western Blot exploits charges of proteins and electric fields to separate species (physics E&M combined with biochem) and the specificity of antibody-antigen interactions. As you get into more complicated techniques (Chromatin Immunoprecipitation, Protein Complementation Assays, etc..) there will be a lot more details to analyze, but that just takes immersion to get a sense of.

Beyond this style of thinking, a lot of MCB background knowledge just comes from reading the literature or reading textbooks/watching videos.
This youtube series is particularly instructive: https://www.youtube.com/watch?v=HCFmr0H6VsE&list=PLGhmZX2NKiNlsqbNuq__7jeedNkdEaZBv

It’s a virology course from Columbia, and it covers not only information on viruses but also how we come to know that information (through techniques). It does a good job at covering everything from the structural biology (NMR, x-ray crystallography) to more macroscopic analyses of cells and viral infections.

Sorry for this really long and rambly response! Hopefully you found this helpful

About the author: ucbr

Leave a Reply

Your email address will not be published.Email address is required.