Science Buddies: "Ask an Expert"

Hi,
I am a high school student in 11th grade taking Independent Research as a class for the first time this year. I originally had many interests mainly within the domains of molecular biology and microbiology, but I have ultimately decided that I wish to do a research project on Prions. I've talked with my teachers about this and have also tried to search for other high school students whom have done a project in the field, but with limited success. My teachers aren't very familiar with prions and the only useful source regarding the feasibility of such a project was a thread on this forum from a past 11th grader also wishing to do research on the topic and who seems to have had success. viewtopic.php?t=12071
Based on the thread, it seems like a project on prions would be doable, but would have to be done using software and not in a wet lab. I know that mammalian prions are far too dangerous to work with in a wet lab as a high schooler, but I had hoped something with yeast prions might be doable. My teachers have advised me to not physically mess with prions of any type, and honestly they're probably right. But I'm not sure what direction to take regarding a digital project on prions. I'm not sure what resources are available to me and how to use them, or what exactly I'm looking to test or do yet. From the aforementioned thread I gathered that a protein prediction software (like maybe I-TASSER or RaptorX?) might be useful, but I'm not sure how to use these or what to do with them.
What resources are available to me, and how can I narrow down my focus to an actual question, testable using the resources I have?

Hi,

You have chosen a highly interesting and important area of research in focusing on prions but as with so many high school projects, you have run up against the difficulties of actually doing experiments to test a hypothesis. Human prions can be deadly and have to be handled under very strict conditions in a molecular biology lab as you say, but you then ask about prions that are specific to yeast.

I did a quick search for safety of using yeast prions but did not find any statement about this in the literature. If you do want to explore this possibility, I suggest that you contact someone in the research compliance division of a university and ask them what their guidelines are for research using yeast prions. If you were planning to work in a university lab then they would be able to help you find the right person to talk to about this project.

If you cannot do the project in a wet lab, there are valid ways of obtaining meaningful and useful data using molecular biology software. In doing a search I came across a very interesting article from 2014 in The Scientist about prions as regulators of normal cellular processes rather than only as disease causers: http://www.the-scientist.com/?articles. ... of-Prions/

Near the end of the article, the author describes some work by researchers at his university, UT Southwestern Medical Center, who discovered that a protein called MAVS, which functions in the human immune response to virus attack, was able to assume a prion-like state (called 'amyloid', like the protein bundles found in Alzheimer's disease). This association of MAVS proteins into prions caused the cell to die but doing this prevented the virus from taking it over and using it to make more virus, so it is actually beneficial.

I haven't read the paper about the MAVS protein but what I wondered was why the researchers suspected that it acted like a prion protein. Does it have a particular amino acid sequence that labels it as a potential prion-producing protein? This might be an area you could explore for a non-lab project on prions. There are existing programs that are free and allow you to search for specific sequences or configurations in a protein. Maybe you could modify one of these to identify potential prion-producing proteins. Scientists who do prion research in a lab could then use your data to target proteins that might have prion-like properties in normal physiology.

I hope this helps you to make a decision about your project. Please post again if you want more information.

Good luck!

Sybee