EPIC symposium provides platform to develop strategies against infectious diseases
CLEMSON, South Carolina – The 5th Annual Cell Biology of Eukaryotic Pathogens (CBEP) meeting was held on Oct. 19-20 at the Clemson Outdoor Lab, bringing together some of the best parasitic and fungal disease researchers in North America for coffee and collaboration.
Hosted by Clemson University’s Eukaryotic Pathogens Innovation Center (EPIC), the meeting is held every year to help researchers make contacts and develop ideas for novel approaches to studying some of the most devastating and infectious diseases in the world, such as malaria, fungal meningitis, dysentery and sleeping sickness.
Professors, research assistants and students came from universities across the nation and Canada to present their latest findings on the cellular workings of parasites and fungal pathogens in the form of talks and poster presentations.
The majority of the poster presentations were given by Clemson students, such as Katherine Floyd, whose research had her knock out a gene known as PPO in Toxoplasma gondii to uncover how it directs the parasite’s growth and virulence factors.
Manuel Fierro, a third-year graduate student at the University of Georgia, centers his studies on the hot-button goal of infectious disease research – the development of successful drug targets. In his presentation, Fierro explained how calcium-signaling affects the growth and egression of Plasmodium, the malaria parasite.
“In a nutshell, my project deals with a protein that has been shown to bind calcium when it goes to the endoplasmic reticulum,” Fierro said. “When I knock this protein down, reducing its expression, it affects the invasion and egress processes of the malaria parasite. So, if you want to find a therapeutic target to attack malaria, I have a great candidate.”
As is the case with most infectious disease research, the key to a curative drug lies in targeting a biological process or cellular component that is unique to the disease-causing parasite.
While Fierro homed in on calcium signaling for malaria, graduate student Hannah Brown from Duke University researches an alkaline response pathway in the fungal pathogen Cryptococcus.
“Cryptococcus is found everywhere in our environment, though usually in pigeon poop and eucalyptus trees,” Brown said. “It likes to grow at a pH of around 4 to 5, but when it’s inhaled into the human lung, it needs to adapt to a more alkaline – higher pH – environment of 6 to 7. That’s what I’m interested in understanding – how can this fungal pathogen adapt to a new environment, infect, and eventually kill its human host?”
By screening and sequencing the Cryptococcus fungi, Brown singled out two cellular components that are sensitive to a higher pH – an enzyme called Cdc50 flippase and a cholesterol-like molecule called ergosterol – for further study.
“We think that a high pH, paired with reducing the ergosterol content in the cell membrane asymmetry will lead to the eradication of the fungus in the lung,” Brown said.
The CBEP meeting even fostered a potential collaboration-in-motion between Zachary Mackey, an assistant professor of biochemistry at Virginia Tech, and Clemson student James Oristian, who researches under EPIC professors Jim Morris and Joshua Alper.
Oristian, a senior in biochemistry, has been working with Morris and Alper to develop a method to isolate dynein, a motor protein, from the parasite that causes sleeping sickness, Trypanosoma brucei.
Dyneins operate like a train on a track; they’re proteins that slide along microtubules within cells, allowing those cells to move throughout the body. In the single-cell of T. brucei and other kinetoplastids, axonemal dynein powers the whipping motion of lash-like protrusions, called flagella. Being that flagella are necessary for kinetoplastids to successfully move into a host, the role of dynein as an initiator of flagellar mobility holds promise as a potential drug target.
If the Clemson team can refine the purification of axonemal dynein from T. brucei, then Mackey, who also studies sleeping sickness, could analyze the protein to uncover other protein interactions. For instance, if a different protein of interest in sleeping sickness – called proliferating cell nuclear antigen, or PCNA – is shown to interact with dynein, Mackey might be onto a new therapeutic target against the disease.
“I’m kind of afraid of dynein because it’s so big,” Mackey said. “So, this could be a natural collaboration, because I can make tons of Tb-PCNA, and we can just ship some down here in the mail, and see if those two actually interact in vitro.”
These kinds of collaborations are what meeting organizers had in mind when they established EPIC’s CBEP meeting almost five years ago.
“When EPIC was just getting started, we wanted to get our name out there and get these kinds of interactions going. The easiest way to do that is to get all of these people in one room, to see that this is a group that’s really focused,” said Cheryl Ingram-Smith, chair of the organizing committee and an associate professor of genetics and biochemistry at Clemson. “The more relationships you build, the more strength you have to generate ideas.”
This annual CBEP meeting was funded by a $10.5 million Centers of Biomedical Research Excellence (COBRE) grant awarded to EPIC in May 2016. Headed by professors Lesly Temesvari and Kerry Smith, the grant aims to amass a team of scientists, with all the necessary infrastructure, to combat infectious disease research.