Hello lovely people of the internet,
Welcome to my inaugural blog post! Today, I’m sharing a little bit about my current research at Carnegie Mellon University. Don’t worry or get intimidated. I wrote this for everyone regardless of their science background. I firmly believe in open science and that includes writing posts for everyone to read and understand. Strap in kids and enjoy the ride!
In the best horror movies the killer is close to you: the best friend you’d never suspect, the kindly old lady, the call coming from inside the house! Candida one of the millions of microbial hitchhikers that live with us humans. Most of us pick up this fungi from our moms as babies. In fact, about 70% of people cohabitate with this yeast and never even notice. But for people with AIDS, cancer or compromised immune systems candida can be deadly. It is the fourth most common hospital acquired infection and even with the best medical treatment about 40% of patients hospitalized with candida infections die.
Now candida isn’t deadly on purpose, it’s trying to survive a stressful environment. Your body can be a surprisingly hostile place for microbes! To stay alive candida changes its whole body, shifting from yeast to hyphae. Yeast are single celled free living fungi. Hyphae are long connected fungal filaments, like a garden hose they can transfer material between connected cells. This HUGE shift is known as filamentation and looking at yeast and hyphal candida under the microscope you’d never guess they were the same thing. Interestingly, only hyphae cause disease, penetrating tissue barriers in your body, exploding immune cells, and oozing a toxin. Think Bruce Banner turning into the Hulk!
What causes mild mannered yeast to turn into destructive hyphae? The genome is a giant cookbook with lots of different recipes (genes) to make all the cellular components. The process of gene expression dictates what components are made under different conditions. Only some recipes are made at any given time. Think about it; you only need an umbrella if it’s raining, otherwise why waste the resources? Sound mixers can turn the music on or off, control the volume, modulate the tone, and make sound come out of different speakers, likewise gene expression includes more than turning a gene on or off – it regulates “how much”, “what kind” and “where” a product is made. Candida yeast and hyphae are genetically identical (same cookbook) but look and act completely different due to differences in gene expression (making different recipes).
In stressful situations, a cell must make major renovations in mere minutes, or it’s lights out for the little guy. During filamentation, stressed candida turns on and off a whole dictionary of genes to stay alive. Imagine your neighborhood is flooding and you only have a few minutes to take apart your house and use it to build a boat! You would need lots of different tools and wouldn’t stop to eat lunch. Likewise, candida has lots of different tools regulating filamentation: expressing stress response genes and pausing expression of non-essential genes. Some ways that candida controls filamentation are well known, but I’m curious about the more mysterious ways it adapts to stress.
Cellular life or death decisions are under tight security. There isn’t one big red button to launch a nuclear missile strike! There are multiple levels of keys, codes, and cross checks before things get post-apocalyptic. Likewise, candida has many layers of checks and balances before inducing the life or death filamentation stress response. If it doesn’t become hyphae fast enough it could be killed by the stress. On the other hand, transitioning to hyphae in the absence of stress could lead to detection and destruction by the immune system. Most scientists investigating how gene expression regulates candida filamentation are looking at one layer of control; I’m looking at a later point of gene expression regulation that we know almost nothing about.
Of course, a single yeast cell doesn’t have a brain to make an active decision the way we do. So, I’m researching the stranger ways candida controls gene expression during filamentation. My research is exciting because it asks: what currently unknown strategies does candida use to shift from yeast to hyphae? The answer could be directly helpful in the doctor’s office. We could get a lot better at telling the difference between people with benign candida hitchhikers (yeast) and folks with infections (hyphae) before they get too sick. We could also use this as a jumping off point for developing new and improved drugs. Instead of killing candida, a new drug could simply coax it back into the yeast form and make it a good roommate again.
However gene expression is controlled during candida filamentation; after millions of years of evolution I guarantee you it’s bound to be more wild, weird, and wonderful than we can possibly imagine.