A Saskatchewan born molecular biologist believes that collaboration is a key in both science and fighting the COVID-19 pandemic. Dr. Nevan Krogan shared his experiences in a virtual presentation to Saskatchewan’s research community hosted by the University of Regina on Tuesday.
Krogan (BSc’97, Msc’99) is an alumnus of the U of R and discussed his work as director of the interdisciplinary Quantitative Biosciences Institute (QBI) at the University of California, San Francisco (UCSF), where he is also a professor.
The Quantitative Biosciences Institute focuses on building global networks and has established itself as an important hub for novel biomedical research and technology development. The QBI has worked on several global collaborations that have brought scientists together, and it was perfectly situated for the formation of the QBI Coronavirus Research Group.
Krogan explained that the QBI is about breaking down barriers or “silos” to respond to the pandemic in an unprecedented way. The scientific vision of the institute and his laboratory is about integration.
He explained that one of the things he dislikes about his chosen field is that it is set up to reward the individual and discourage collaboration
“What we have seen especially in this pandemic is how fast we can move when we break down these silos, these are silos between different laboratories, between different institutions around the world and between academic laboratories and large and small pharmaceutical companies,” Krogan said.
Krogan’s research focuses on developing and using unbiased quantitative systems approaches to study a wide variety of diseases with the ultimate goal of developing new medicines or cocktails of medicines.
They are focused on analyzing genes using various methods. They are also using chemical biology approaches to identify drugs and compounds that could potentially have therapeutic value. They want to interface the approaches and use the research in many different disease areas. They have been doing cell mapping on cancer cells, psychiatric cells and host pathogen cells.
“And we have been focused on a number of different pathogens over the years focusing on viruses and bacteria and one of the centrepieces of our work is the generation of protein interactions using the different pathogenic proteins,” he explained
They have studied pathogens including HIV, Ebola and Influenza among others. These maps usually take a number of years to complete but the map for SARS-CoV-2 human protein interaction was generated in a matter of weeks.
“To me it was a testament to the collaborative spirit that went into this effort from scientists here at QBI-UCSF as well as scientists around the world,” Krogan said.
Krogan was joined by Jacqueline Fabius, Chief Operating Officer for QBI. Fabius heads a number of initiatives including establishing relationships and collaborations around the world. She explained that the QBI is an institute in the UCSF with 103 affiliated labs doing quantitative research that is based on the idea of discovery science.
“We are well known for our cell mapping initiative which Nevan just spoke to you about. We are also known for our focus on young scientists and the empowerment of women,” she explained.
The QBI creates a culture of collaboration. Each one of the labs already has nearly 100 scientists already involved. She explained that they treat the world like they treat mapping of cells to create the collaboration activities.
“It was not a big leap to move into formal collaboration with the scientists around the world who showed great enthusiasm towards this and at this time we have a number of established agreements and collaborations with many places around the world in Germany, Ireland, France, Nigeria, Poland, Israel and the UK to name a few,’ she said.
They also worked with an institute in France and the coronavirus research group was formed out of taking action in collaboration.
The Research Group is made up of 42 leading laboratories, involving hundreds of scientists within the QBI, as well as laboratories in France, England, Germany, Scotland, New York, Seattle, Montana, North Carolina, San Diego, and more, are combining their efforts, technologies and expertise to fight the coronavirus pandemic.
“One of the things that we are focused on is trying to come up with host directed therapy for the virus,” Krogan said.
Led by Krogan, the newly-formed QBI Coronavirus Research Group is bringing together expertise in biochemistry, virology, structural, computational, chemical and systems biology to understand how SARS-CoV-2 hijacks human cells for its own replication.
“We are trying to understand which human proteins and genes the virus needs to infect our cells and try to identify drugs or compounds that would impinge upon or target those human proteins and hopefully then we could identify antivirals that way. It’s a host directed therapy to try to combat this virus and there is advantages to this. You don’t have to worry so much about resilience viruses,” he explained.
The goal is to assist in the rapid development of treatments. The presenters will explain the recent discoveries made by the QBI Coronavirus Research Group and what this could mean for future treatment of COVID-19.
“We and others have shown that different viruses target similar genes and proteins in our cells. So the idea is if we could come up with a host directed therapy for COVID-19 it could be applicable for COVID-22 or COVID-24,” he said.
He explained that they may have been the first group to synthesize the genes. They then went on Twitter with the UCSF lab account that they had this information and would be happy to share it no strings attached.
“There were no lawyers at work anyway so that didn’t matter so we would say feel free to distribute as you see fit. And in a matter of a few weeks we were able to send these genes to over 370 labs in over 40 countries. These genes, the viral genes that we synthesized spread around the world a lot faster than the actual virus did and we are quite proud that we were able to send these out to the scientific community to help expedite research on this virus so that we could all come up with hopefully ways to combat it,” Krogan said.
The goal was to generate the map and then make predictions about which drugs and compounds would inhibit the human proteins they think the virus would need.
“The virus cannot exist by itself it needs our genes in order to live and replicate and infect us. So the challenge here is to identify all of the human genes and proteins that the virus needs to infect our cells,” he explained.
They identified 69 different drugs or compounds that they thought would target at least one of these proteins. They argue that one or more of these would have antiviral effects. They are looking into a number of drugs for COVID-19.
There were about 10 top drugs found at the end of June and three clinical trials at the time that had started based on them. Since the end of June there has been more clinical trials that have been started.
Their future work will continue transitioning into clinical trials and trying to find a drug cocktail that will be effective which will be similar to that used for HIV according to Krogan.
“I’m hoping we have at least one of those drugs in our mix and we are combining them together with each other and we are also combining with other drugs people are finding as well as with drugs directly targeting the virus,” Krogan said.
The key is that it is an academic and industry collaboration and the collaboration is key for Krogan.
“You don’t just snap your fingers and get people to work together. We have been working very hard at QBI at establishing relationships over the last several years through symposia, through creative events, through attempting to find money to bring scientists together. So I would argue as a point was made during the seminar here we are in a perfect to respond to that. So you can’t just snap your fingers and make that happen it took a lot of work to put in the foundational efforts there. And now the challenge is how do you go forward,”
He coordinates efforts from his office in San Francisco coordinating efforts all day over Zoom.
“It’s incredibly efficient but it is incredibly complicated as well,” he explained.
They are trying to keep the infrastructure in place for future collaboration. The work is intense and Krogan believes that the scientific system discourages collaboration and rewards the individual through benefits like tenure, grants and even the Nobel Prize.
“So one person gets the Nobel Prize, one person gets tenure, one person gets a grant, it is never a group, it is rarely ever a group. And this really discourages the young scientists from getting involved in collaborations they are very protective and secretive. So what we need to do is have a system where large awards go to, why not 300 scientists,” he explained
He explained that collaboration needs to be seen as a positive thing in the scientific community.
“In order to sustain this I think we do need to change a lot of things but now is the time to change things in the context of a pandemic, you can start from square one. So I think the challenge for the scientific community is to change a lot of things and hopefully we can do that so we can work as hard and as fast in other disease areas maybe slightly different intensity, maybe slightly lower intensity but not too much lower,” Krogan said.
Krogan hopes to see new drugs by the end of 2020 after more clinical trial data comes in over the next few months.
