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Studying prions’ “molecular memory”

Alan Itakura

Nov 14 2017

Alan Itakura is a Biology graduate student in ChEM-H Faculty Fellow Dan Jarosz’s lab. He switched from a photosynthesis lab to a yeast lab at the start of this year to study some unusual aspects of prions. He spoke with postdoc Adam Idoine about his journey so far and where it may lead in the future.

By Adam Idoine

Your new lab studies prions; can you explain what a prion is?

Prions are proteins that take on an alternative shape, meaning they have changed, semi-permanently, from their usual 3D structure. They bind to non-prion forms of themselves and force them to change to the prion form, perpetuating themselves throughout the cell and its progeny. Prions are unique because, instead of DNA being the heritable element, it is the protein in the prion conformation – a paradigm shift from the central dogma of biology. They’re a sort of molecular memory that exists beyond the genome.

Not all proteins have prion forms, but we are realizing the phenomenon is more common than we initially suspected. We used to think prions were an aberration, confined to diseases like Alzheimer’s and mad cow disease; but now we've realized that they play a role in normal biology.

Prions can help cells adapt to their conditions. One example of this is a prion in yeast, [GAR+], which allows yeast to use energy other than glucose to grow. We’re using yeast as a model organism to understand the basic biology of another interesting prion we have identified.

I understand your favorite prion is unusual because it’s not associated with disease?

I have been working with Anupam Chakravatry, a post-doc in the lab, on a protein that is known to degrade RNA in its normal, correctly-folded form. This RNA degradation is a process that is important during the development of many organisms. We’re looking at how the prion form of this protein affects its ability to degrade RNA. In yeast, we think the prion influences the cell's decision to divide asexually or sexually, a first for prion biology!

How do you create a yeast with a prion?

I force cells to make prions by making them produce a lot of the normal protein in a short time window. When you increase the number of proteins, there’s a higher chance that some are going to randomly fold into prions. We compare the cells with prions to normal cells; the cells are genetically identical, but they behave differently due to the presence of a prion.

You were working in another lab for two years of your PhD before you joined Dr. Jarosz’s lab? Can you tell me how the transition has been?

The change in thought processes has been humbling, because I had just gotten to the level in my previous lab where I felt I was becoming a relative expert, even amongst my peers in the lab. To have that complete reset in the middle of my PhD has been a difficult transition, although everyone has been really supportive and helpful.

How do you feel your research fits into the grand scheme of things?

I think it's thrilling to be the first person to know some intrinsic truth of nature, and to be the first person seeing the data that confirm your suspicions of how the world around us works. That's an exhilarating experience. I also contemplate that I’m part of a larger bet by society to cast a wide net and fund a lot of research without knowing which experiments will be relevant to society. This bet is necessary to maximize the odds of funding research that does end up benefitting society.