In the nine months since the first cases of COVID-19 were noticed in Wuhan, China, the virus has spread around the globe and infected over 22 million people. As with all emerging infectious diseases, we often find ourselves with more questions than answers. However, through the tireless work of researchers, doctors and public health officials worldwide, we have learned a lot about the virus, how it spreads and how to contain it.
Gayetri Ramachandran taught her first university class during the COVID-19 pandemic. While the online course was successful overall, it was a strange experience to teach without being able to see the students.
“If you’re giving a seminar and you can’t see the other person, it’s extremely difficult,” says Gayetri, a postdoctoral researcher at the Institut Necker Enfants Malades in Paris, France. “If they’re sleeping, I can’t see them. It’s fine, you can sleep, but if I can’t see that you’re sleeping, then I can’t get that feedback in real time.”
Earlier this summer, Gayetri had another opportunity to give an online presentation. Before the COVID-19 pandemic disrupted travel plans, she was scheduled to visit the Promega Headquarters in Madison, WI, to tour the facilities and meet with R&D scientists. Instead, Gayetri presented her research to a group of Promega scientists in the first Promega Virtual Customer Experience Visit.
If you’re preparing to return to the lab for the first time in months, there’s never been a better time to make your lab more sustainable.
Earlier this year, the COVID-19 pandemic forced thousands of labs to temporarily shut down. As restrictions are lifted in many areas, scientists are slowly resuming research. However, reopening a lab after months of closure will require a lot of cleaning and organizing, much like a fresh start. This presents a valuable opportunity to evaluate your lab’s practices and identify ways that you can reduce your environmental impact.
Many research labs around the world have temporarily closed their doors in response to the COVID-19 pandemic, while others are experiencing unprecedented need for reagents to perform viral testing. This urgency has led many scientists to make new connections and build creative, collaborative solutions.
“In labs that are still open for testing or other purposes, there’s certainly heightened anxiety,” says Tony Vanden Bush, Client Support Specialist. “I feel that right now, I need to help them deal with that stress however possible.”
Last week, Tony was contacted by a lab at the University of Minnesota that was preparing to serve as a secondary COVID-19 testing facility for a nearby hospital lab. The two labs needed to process up to 6,000 samples per day, and the university lab was far short of that capacity.
Jonathan Campbell, PhD, asked me to write that he is taller and a bit more handsome than most scientists. I will neither confirm nor deny those assertions, but I will acknowledge that Dr. Campbell has a unique way of describing his recent collaborations and research on metabolism and Type 2 diabetes.
“The rest of the world has been thinking that it’s almost like the emperor has no clothes,” he says. “But we’re the guys who came right in and said ‘Hm, that dude’s naked.’”
On March 13, only a few days before the COVID-19 pandemic caused widespread shutdowns in Wisconsin, Jon visited the Promega headquarters in Madison, Wisconsin to meet with R&D scientists and discuss opportunities for new technologies. Over the course of a few hours, Jon and his collaborator Matthew Merrins, PhD, demonstrated how their research challenges dogma and could fundamentally change our understanding of postprandial metabolism. For five decades, the paradigm of glucose control focused on a model that positioned insulin and glucagon as diametrically opposing forces to raise or lower glycemia. As Jon states, things did not always add up.
“For years, everybody has been saying ‘Glucagon is the antithesis of insulin,’ right? Insulin is a good guy. It makes glucose come down. Glucagon is a bad guy. It makes glucose go up. And these two are in this cosmic battle against each other over the control of glycemia. Well, we asked, ‘Why do the beta cells that secrete insulin have glucagon receptors?’ And as you follow the breadcrumbs, you find that these two things are actually working in cooperation. Without that cooperation, the whole thing falls apart,” Jon says.
The Incretin Effect
In addition to exploring the complex biology of glucagon, Jon’s lab studies the Incretin Effect, a mechanism by which the gut influences the secretion of insulin in the pancreas. Past research revealed that rises in blood-glucose matched closely whether glucose was administered orally or intravenously. However, the amount of insulin secreted was 3—4 times higher following oral intake. This is a result of the actions of GLP1 and GIP, the two major human incretins. GLP1 and GIP bind to G-protein coupled receptors in the beta cells of the pancreas to induce insulin secretion. Insulin then acts to promote glucose uptake, reducing glycemia. Many researchers believe that dysfunction of the incretin mechanisms contributes to the reduced insulin secretion seen in individuals with Type 2 diabetes.
“If we can understand the mechanisms of the incretin effect,” Jon says, “We may be able to understand the pathophysiology driving Type 2 diabetes. My hope is that people are going to realize that diabetes is not just a glucose disease. Maybe we have been looking at this too much from a glucose-centric viewpoint. Clearly, glucose is a big problem with diabetes, but it’s not just glucose. This is a metabolic disease, and in order to understand how to fix a metabolic disease, you need to look at all the metabolites and the way overall metabolism is dysregulated.”
Research on the incretin effect has already supported the development of two new classes of drugs for Type 2 diabetes: GLP1R agonists and DPP4 inhibitors (DPP4 is an enzyme that degrades GLP1).
“We collaborate with industry quite a bit, especially pharmaceuticals. We are helping them understand the mechanism of action by which their drugs may work, and that funding has allowed us to expand and grow our program a lot in our first five years. I like to bridge that line between basic and translational science—translating basic science into the clinic.”
The Search for New Technology
Jon wasn’t visiting Promega in mid-March with the goal of seeing the world before COVID-19-related travel restrictions were announced. He’s constantly looking for new collaborations in which both parties can bring something unique to the table. Jon was one of the first to try the new Lumit™ Insulin and Glucagon Immunoassays, which he says are easier to use and have produced better results in his work with glucagon than radioimmunoassays or ELISAs.
“People like Promega scientists say they have a new technology, and they’re looking for someone to try it out it in real-world situations. I don’t have that kind of technology, but I know how to apply it, so there’s a lot of value there. It’s a no-brainer to talk to people about how we can find synergy when the two of us both bring something like that to the table. For some applications, the Lumit™ assays are blowing out whatever we can do, and they’re also incredibly easy to use. So that was a significant improvement in our workflow.”
When asked what he hopes to accomplish in the next few years, Jon similarly points to innovative technology and techniques.
“We have to say, ‘What’s the next innovative step forward, and what new tools can we bring?’ We need to figure out new ways to interrogate the systems that we’re interested in. Then we can start to strip away new biology. If we ask the right question and we answer definitively, we’ll end up with three more questions. Which is great, because we’ll always have more work to do.”
Lumit™ Immunoassays provide a simple and fast alternative to conventional immunoassay methods including sandwich ELISAs and Western blots. Learn more here.
Working on diabetes research? Read more about Promega assays to measure insulin activity in real time.
A protein first purified and sold by Promega almost four decades ago has emerged as a crucial tool in many COVID-19 testing workflows. RNasin® Ribonuclease Inhibitor was first released in 1982, only four years after the company was started. At that time, the entire Promega catalog fit on a single sheet of 8.5 × 11” paper, and RNasin was one of the first products to draw widespread attention to Promega. Today, the demand for this foundational product has skyrocketed as it supports labs responding to the COVID-19 pandemic.
What is RNasin® Ribonuclease Inhibitor?
RNA is notoriously vulnerable to contamination by RNases. These enzymes degrade RNA by breaking the phosphodiester bonds forming the backbone of the molecule. To say that RNases are everywhere is barely an exaggeration – almost every known organism produces some form of RNase, and they’re commonly found in all kinds of biological samples. They’re easily introduced into experimental systems, since even human skin secretes a form of RNase. Once they’re present, it’s very hard to get rid of them. Even an autoclave can’t inactivate RNases; the enzymes will refold and retain much of their original activity.
RNasin® Ribonuclease Inhibitor is a protein that has been shown to inhibit many common contaminating RNases, but without disrupting the activity of enzymes like reverse transcriptase that may be essential to an experiment. It works by binding to the RNase enzyme, prevent it from acting on RNA molecules. This is important for ensuring that RNA samples are intact before performing a complex assay.
As we continue navigating the challenges presented by COVID-19, several research areas are crucial for helping us slow the infection rate and ending the pandemic. Advanced testing methods, such as antibody testing, help us understand and predict how the virus will spread, which can inform policy decisions. Effective therapeutics will influence clinical outcomes for individual patients, and several drugs are already being tested or administered. However, an effective vaccine against the SARS-CoV-2 virus is perhaps the most important tool we can use to protect individuals and populations from COVID-19.
Over 90 vaccines against the SARS-CoV-2 virus are currently in development around the world. While there are many different types of vaccines, the overall goal is to create long-lasting protective immunity by stimulating the production of specific antibodies. As these vaccine candidates are further characterized, monitoring ADCC activity can provide important insights into their potential efficacy.
Since Wisconsin issued a Safer at Home order on March 25, I have been leaving my home exactly once a week. Every Tuesday morning, I drive to a small town outside of Madison to spend an hour monitoring a nest of bald eagles. I’ve been volunteering for Bald Eagle Nest Watch since the beginning of the year, and three weeks ago I got my first look at two newly hatched eaglets. Over the past few weeks, I’ve found that my time at the eagle nest is a wonderful relief from the stress of the pandemic and the confinement to my home.
I’m not the only person escaping to natural spaces for relief during the widespread lockdowns in response to COVID-19. Parks have been filled with people taking daily walks and enjoying fresh air when there are few places indoors they can safely go. Besides encouraging many people to visit local parks and forests, the COVID-19 pandemic has revealed many complexities of humanity’s relationship with the environment. The severe drop in human activities has resulted in decreased air pollution, as well as fascinating changes in wildlife behavior. However, the pandemic is also an important reminder that the environmental impact of human activity has drastic consequences for global risk of infectious disease. This Earth Day, it’s the perfect time to pause and examine how the COVID-19 pandemic and the natural world are influencing each other for better and for worse.
Implementing a new high-throughput (HT) nucleic acid purification workflow or scaling up an existing workflow presents many unique challenges. To be successful, the chemistry and liquid handler must be perfectly integrated to fit your lab’s specific needs. This involves configuring the instrument deck, optimizing the assay chemistry, and programming the instrument.
When you’re facing a sudden spike in sample throughput demand combined with unprecedented urgency, those challenges can often become overwhelming. Even in times of crisis, Promega scientists are prepared to support labs facing challenges with HT workflows, regardless of your instrumentation platform.