You can’t study for them, and they won’t affect your GPA, but disease tests are vital to fighting infections. They certainly caught the interest of Dr. Camilo Duque Velasquez, who started his education with a Bachelor of Science degree focused on biology at the University of Antioquia in his hometown of Medellín, Colombia. He soon became intrigued by the idea that proteins could be infectious when they take the form of prions (abnormal pathogenic proteins that are transmissible).
“Early on in my biology education, I became interested in viruses causing disease in people and animals,” said Duque Velasquez. “They are very diverse pathogens, composed of nucleic acids covered by protein envelopes that each virus can reproduce when it infects natural hosts.”
In the middle of microbiology class one day, his professor started talking about a protein that was infectious and could destroy the brain, which – not surprisingly - caught his attention. Shortly thereafter, he attended a seminar at a neuroscience lab that focused on describing a potential case of prion disease.
“When I asked how the diagnoses were confirmed at the molecular level, they said samples are shipped to another laboratory in the United States. I wondered why nobody in Colombia was doing that job, and it clicked in my mind that I could do it myself.”
Collaborating with a supervisor in the veterinary department, he wrote a grant proposal that was accepted by the Colombia Science Foundation (Colciencias), allowing him to establish the diagnostic assays required for detection of prions in post-mortem brain tissue (detection of prions in thin slices of brain and protein extracts from suspected cases).
A walk on the wild side
The Colciencias grant also enabled him to visit the United States, where he completed an internship at the USGS National Wildlife Health Centre in Madison, Wisconsin. It was there that he received training on performing diagnostic assays in the lab, knowledge he took back to Colombia and applied to previously untested samples. As an intern, he also connected with his current supervisors, leading to an offer to attend the University of Alberta and complete his PhD in animal sciences, which he did in 2017.
“I work primarily on studying the diversity of prions in cervids such as deer, elk and moose. We are comparing their biological signatures and the transmission properties of prions from wild deer, using in vitro and in vivo assays to evaluate if we are dealing with the same type of prions or with different strains. This is a long process because these diseases have a long incubation period.”
His PhD thesis centered on the evolution of Chronic Wasting Disease (CWD) prions that infect cervids. The major finding of his research pointed at deer polymorphisms (genetic variations) that can change the prions that infected them (it makes them evolve). This may have a major impact on the prion’s ability to transmit to other deer that are considered to be genetically resistant or to other wildlife species, livestock or even humans.
Having completed his PhD, the researcher’s focus is now centered on CWD, a condition that intrigues him because it represents one of the most dynamic prion infections, with potential hazardous effects on wildlife, agriculture and public health.
No time to waste
“CWD exists in the wild and is highly contagious,” said Duque Velasquez. “I’m fascinated by the idea that prions can evolve, and I want to understand the steps leading to their evolution that result in new prion strains with new infectious properties. I believe this could help explain why prions develop resistance against candidate drug compounds for treating prion diseases.”
He is also curious about how prions induce neurodegeneration and how different strains produce different disease pathologies; lesions produced in the brain by one strain differ from those produced by another.
Armed with a keen interest in prions and CWD, Duque Velasquez started working as a post-doctoral fellow on a project partly funded by Genome Alberta entitled “Systems Biology and Molecular Ecology of Chronic Wasting Disease”. This large scale, collaborative effort involving several Alberta laboratories aims to understand biological and environmental aspects of CWD via a range of scientific approaches to help delineate responses to stop the spread of the disease.
“The principal investigator on the project was part of my graduate committee and is now my supervisor. During my graduate research we started working on some CWD samples from experimental infections previously performed on deer.”
Those samples were perfect for him as they originated from genetically different deer infected with the same CWD prion isolate. This enabled him to ask questions like whether the genetic differences between deer actually change the prion, and it turns out that they do.
They wound up isolating a new CWD prion strain, which prompted them to write up various research proposals to obtain funding.
“I am involved with one small part of the project, characterizing the prion strain diversity using samples from wild cervids. The larger study includes searching for genes that are expressed differently in infected versus non-infected cervids, polymorphisms associated with resistance, the interaction of prions with soil components, metabolites that can indicate infection and social aspects related to the spread of CWD.”
Straining for results
As part of his work on the project, Duque Velasquez has found some preliminary evidence indicating the existence of different strains of CWD in Canada. One of his colleagues in the project recently published her findings on the effects of humic acid - a chemical produced by decaying plants – and its ability to degrade prion infectivity.
If knowledge is power, the information he and his colleagues are gathering with this project could prove a powerful tool in the fight against CWD.
“From the standpoint of wildlife and public health, we are identifying the prion strains infecting cervids in the wild and on farms. This is a critical first step in developing tools to comprehend the prion agents responsible for CWD epizootics [disease events in nonhuman animal populations analogous to an epidemic in humans]. This would allow us to test the efficacy of decontaminating agents like humic acid, and vaccine candidates, against the prion strain in circulation. Previous attempts by other laboratories to develop a vaccine have not been successful.”
One lab of the multi-disciplinary team on this project is currently forging a vaccine for prion diseases.
“We hope to investigate the vaccine’s ability to protect against multiple disease strains. The limitation is the high cost of bioassays of this magnitude in deer or even transgenic mouse models.”
Among other things, Duque Velasquez enjoys the ability to collaborate with fellow researchers towards a common goal.
“We are working with a lab in Calgary and kind of reviewing each other’s findings. We share samples and compare the results to see if they match, and when they do, it tells me I’m not fooling myself because the other person saw exactly what I did.”
This study has been a real eye-opener so far, as researchers began with the assumption that there were only two strains of CWD, and have now identified at least five.
During those rare moments when he is not in the lab, Duque Velasquez enjoys swimming, tackling the climbing wall, cycling in the river valley and joining his colleagues for drinks on Fridays.
Though he is intrigued by the prospect of one day being his own principal investigator with his own lab, he recognizes that it is a steep hill to climb, and is happy with his current course of research.
“I like spending time in the lab, getting the gloves on and doing experiments. I am in the perfect place to study prions and particularly CWD, which is a big problem that is not going away. The disease prevalence keeps increasing in animals and showing up in new places. There are still many questions to be answered and progress to make, so I want to keep this as my focus for now.”