“Today is certainly a great day for Promega R&D, but it is also a great day for science.”
Gary Tarpley, director of Research and Development at Promega closed his remarks for the ground breaking of the new Promega Research and Development Center in Fitchburg, WI, with those words.
With the ground breaking on this new R&D facility, Promega makes a $190 million, long-term investment in science.
Think back to your grad school days. Think about a time when you were struggling with challenges either inside or outside the lab. Maybe you dealt with failed experiments, a toxic lab culture or mental health problems. For graduate students, these have been real, everyday experiences for as long as anyone can remember. The Hello PhD podcast, hosted by Joshua Hall and Daniel Arneman, aims to address those problems. We’re excited to announce that beginning with Episode 94 (released June 11, 2018), we are now partnering with Hello PhD to promote their mission to support young scientists in training.
Hello PhD will be celebrating its third anniversary in July 2018, and in the past three years they’ve covered topics from grad school admissions to choosing a career path, and everything in between. They’ve interviewed post-docs, science communicators and students with interesting experiences to share. The most popular Hello PhD episode ever, “When Research Sucks,” discusses what to do when research starts to drag you down. After 94 episodes, they still haven’t lost sight of their mission to make the grad school experience better for both current and future students. Continue reading “Hello PhD + Promega: Partnering to Support Young Scientists”
My twin daughters are finishing up their 10th-grade year next month, finding themselves smack in the middle of their high school experience, and discussions of classes, colleges and careers are increasing in frequency in my household. (It’s cliché, but I have to say it… Where does the time go?) As the girls begin to ponder their future, my husband and I are encouraging them to gain real-life insight from adults who work in fields they’re curious about. It’s never too early to get a first-hand perspective.
One of my girls has known from a pretty young age that she wants to pursue something in STEM, and likely the “S” in the acronym. Her schedule happened to be open the night a few months ago that one of my Promega colleagues, Senior R&D Scientist Danette Daniels, was speaking on a panel sponsored by the University of Wisconsin – Madison chapter of Graduate Women in Science. My daughter wasn’t sure about how she’d be received as the only high school student in the room, but she agreed to go with me anyway. Besides, I told her, they’re serving pie.
The six women on the panel represented a huge variety of avenues (academic to industry), specialties (biophysics to geology) and professional styles. During introductions, one panelist declared, “I had a job in a lab and was depressed. When I was stuck in a library all day, I was totally excited.” She now works with an organization to recruit more women into STEM fields. The woman sitting beside her runs a research lab and declared, “I love the bench quite a bit, and I don’t want to be in an office reading!” Continue reading “Inspiring the Next Generation of Scientists”
There are 3 billion (3,000,000,000) bases in my genome—in each of the cells of my body. Likewise, Johanna, the writer who sits next to me at work also has 3 billion bases in her genome. Furthermore, our genomes are 99% the same. Still, that’s a lot of places where my genome can differ from hers, certainly enough to distinguish her DNA from mine if we were both suspected of stealing cookies from the cookie jar. The power of discrimination is what makes genetic identity using DNA markers such a powerful crime solving tool.
The completion of the human genome project in 2003 ushered in a tremendously fast-paced era of genomics research and technology. Just like computers shrank from expensive, building-filling mainframes to powerful hand-held devices we now call mobile phones, genome sequencing has progressed from floor-to-ceiling capillary electrophoresis units filling an entire building to bench top sequencers sitting in a corner of a lab. The $99 genome is a reality, and it’s in the hands of every consumer willing to spit into a tube.
Commercial DNA sequencing services are promising everything from revealing your true ancestry to determining your likelihood to develop dementia or various cancers. Is this progress and promise or is it something more sinister?
As it turns out, that isn’t an easy question to answer. What is probably true is that whole genome sequencing technologies are being put into the hands of the consumer faster than society understands the ethical implications of making all of this genomic information so readily available.
We were inspired by a letter we recently received from one of the recipients of the Promega International Scientific Internship Scholarship. The scholarship supports undergraduate students at the University of Wisconsin – Madison. who are undertaking an international internship aimed at using science to improve the quality of life in the world. Students from all scientific fields are eligible but preference is given to those whose internships use molecular biology techniques. Students must be based in a country other than their own for at least six weeks and cannot be in a country where the recipient has already spent significant time.
Sydney Roberts, a junior at UW Madison majoring in Community and Nonprofit Leadership with a certificate in Global Health, was awarded the Spring 2018 Promega scholarship. As a result, she’s spending her spring a long way from her hometown of Cedarburg, WI. Sydney is currently working in Kabale, Uganda, a town in the southwestern part of the country near the border of Rwanda, as an intern with the Kigezi Healthcare Foundation (KIHEFO).
KIHEFO operates a primary care clinic, HIV/AIDS clinic, Nutrition and Rehabilitation center, and works with rural community groups. Sydney is supporting local staff members as they treat clients, provide counseling sessions for families affected by disease, and work on global health initiatives that support prevention of these diseases and health complications. She has only been in Uganda for a few weeks, but she says her experiences have already been life-changing. Continue reading “Letter from Uganda: A Promega International Internship Scholarship Recipient Shares her Experiences”
In February 2018 we wrote about a resurrection effort to bring the then endangered black-footed ferret back from the brink of extinction in western U.S. This effort was undertaken by the U.S. Fish and Wildlife Service, with assistance from Revive & Restore and partners ViaGen Pets & Equine, San Diego Zoo Global and the Association of Zoos and Aquariums.
On February 18, the U.S. Fish and Wildlife Service announced announced the successful cloning of a black-footed ferret, introducing the world to a 38-day-old black-footed ferret kit “Elizabeth Ann” cloned from cells of a female ferret that died in 1988.
Cells from ferret, “Willa” were preserved by freezing, and when somatic cell nuclear transfer (SCNT) became a possibility, Willa’s cells were used to create Elizabeth Ann, the kit born just over one month ago.
Before Elizabeth Ann’s birth there were upwards of 1,000 black-footed ferrets alive in the western U.S., but they were all descendants of just 7 ferrets, and thus genetically very similar.
Analysis of Elizabeth Ann’s genome has revealed more than three times the genetic variants found in the existing wild U.S. ferrets. This means that if she is able to reproduce, her contribution to the genetic diversity of wild ferrets would be huge.
Interested in learning more about ferrets and the challenges they’ve faced in surviving and thriving in the wild? Below is our original 2018 blog with those details. Don’t miss the video clip of a young black-footed ferret doing the “weasel war dance” (below).
Recently, I had the opportunity to attend a fascinating symposium held at Promega featuring conservationist Steward Brand, where he described some of the projects developed by his foundation, Revive & Restore.
The organization’s mission is to apply emerging biotechnology techniques to endangered and extinct species with the intent to increase genetic diversity, provide disease resistance and facilitate adaptation to changing climates. Although the overall message of enhancing biodiversity through the application of new genetic technology was inspiring, the project that resonated most for me was related to the plight of horseshoe crabs.
Horseshoe crabs, often referred to as living fossils, include four extant species with origins dating back about 450 million years. Although they look like crabs, they belong to their own subphylum and are more closely related to spiders. When horseshoe crabs spawn, they leave their usual habitat on the ocean floor and migrate to shore in large numbers. As a result, they have been exploited for bait and fertilizer for decades.
Enter endotoxins, an indicator for bacterial contamination in biologicals, drugs and medical devices. U.S. Food & Drug Administration regulations dictate that finished products be tested for the presence of endotoxins. These pyrogenic compounds, found in the cell wall of Gram-negative bacteria, can cause fever and affect a wide range of biological activity, possibly leading to aseptic shock and death. The most common method for testing is the gel clot and Limulus Amebocyte Lysate (LAL) Test.
I first learned about the LAL test during graduate school, where it was presented as a ubiquitous and standard requirement for testing bacterial contamination in injectable drugs. I remember being fascinated that horseshoe crabs (Limulus sp.), contain a substance that could be used to detect endotoxins. Although the instructors mentioned the need to collect blood from horseshoe crabs in order to produce the test, the method or scale of this harvest wasn’t discussed, nor were the true costs of using this method of endotoxin testing.
The LAL test has served as a faster, more inexpensive endotoxin testing replacement for the rabbit pyrogens test for the past 35 years. Every year during mating season horseshoe crabs move to shallow water, where they are removed in huge numbers. (To get an idea of scale for the harvest and read a much more comprehensive investigation of the issue, check out this article in The Atlantic, which features an archive photo of Delaware Bay horseshoe crab harvest from 1928—for fertilizer, not pharmaceutical testing.)
After collection, the crabs end up in a lab where up to 30% of their blood is drained from a needle stuck in tissue around their heart. The LAL is extracted from the blood and can yield a product worth up to $15,000/quart. In order to avoid recollection, the crabs are returned to the ocean far from the shore where they were collected a few days before. Although it’s estimated that only 10-30% of these crabs die as a result of the process, there are indications that the horseshoe crab population and their ecosystems are impacted in other ways.
Researchers at the University of New Hampshire and Plymouth State University used accelerometers attached to recently bled female horseshoe crabs to test the hypothesis that harvesting for LAL was affecting their ability to spawn. While the research supported previous estimates with a death rate of 18%, females were found to be less likely to mate after being bled.
During his talk, Brand shared results from a study still in review that confirm the effect of over-harvesting Limulus on the survival of long distance migratory shorebirds. These birds synchronize their migration with horseshoe crab spawning, which provides a needed feast of eggs before the homestretch of their journey. Along with other ecosystem threats from climate change, the accelerated decline in the horseshoe crab population and dependency of migratory birds will likely to lead to a devastating ecological domino effect.
Fortunately, a synthetic alternative to LAL, recombinant factor C (rFC), has been available for nearly 20 years. Alas, there has been no significant shift by pharmaceutical companies away from the test based on horseshoe crab blood. rFC was patented and licensed to one company, Lonza, which Brand posited as one reason for the reluctance of drug companies to adopt its use.
Obviously, relying on one source for an essential testing reagent with no competition to temper cost is quite unattractive. But that argument has less bearing now that the patent is scheduled to expire in a few months, opening the door for additional manufacturers and creating an economic incentive for switching to the synthetic test.
Another reason may be that implementing a new test would require additional resources to validate the synthetic test for products that are already being tested with the LAL. Since the LAL has been specified in FDA guidance documents on endotoxin testing for decades, quality standards for existing products are based on the LAL, limiting momentum to change.
If both tests offered the same benefits, these arguments would make sense; however, research by one of the discoverers of rFC, Jeak Ling Ding of the National University of Singapore, shows that in many respects rFC is more efficacious than LAL. Since the raw material for the LAL test depends on an organism, there is seasonal variation in the components of the processed blood that must be taken into account. The reaction of the LAL also depends on a cascade of multiple compounds that can be affected by temperature, pH and proteins—leaving the test vulnerable to false positive results.
Although Eli Lilly is the only pharmaceutical company to date to use rFC in place of LAL, It seems the tide may be turning. According to Brand, others are interested in making the transition. It seems foolish not to, given the source for LAL shows signs of dwindling due to overexploitation. Perhaps pharmaceutical companies are beginning to see the value of a “slower/better” philosophy (the cornerstone of the Long Now Foundation, another brainchild of Brand’s), rather than “faster/cheaper.” I have certainly gained a new perspective on endotoxin testing and a deep appreciation for the work of Brand and his foundation.
Does your organization use the LAL test? What is preventing you from switching to the synthetic alternative? Let us know!
The Foundation for Food and Agriculture Research (FFAR) announced on November 30 that they are awarding $1M to a project based at the University of California, Davis, to study protein kinases of rice plants. The team is led by Dr. Pamela Ronald, a leading expert in plant genetics who has engineered disease- and flood-resistant rice. This project aims to address the growing agricultural problem of water scarcity by gaining a better understanding of the role kinases play in enabling drought-resistance. Promega will be supporting this research by providing NanoBRET™ products to help characterize kinase inhibitors.
Principal Investigator Pamela Ronald, Ph.D. Photo Credit: Deanne Fitzmaurice
The research team will begin by screening over 1,000 human kinase inhibitors to determine which ones do interact with the plant kinome and, if applicable, which kinase(s) they inhibit. Once the compound library has been established, the team will assess the inhibitors’ phenotypic effects on rice to identify kinases that, when inhibited, positively impact root growth and development. The long-term goal is to use these findings to engineer drought-resistant rice.
Amani working in the laboratory of Dr. McFall-Ngai’s as a high school Youth Apprentice
Amani Gillette, a junior from LaFollette High School in Madison, started the Biotechnology Youth Apprenticeship Program (YAP) in Fall Semester, 2010. An outstanding youth apprentice (YA) throughout her two years in the program, she excelled in both the specialized laboratory course at the BTC Institute and in her work site research under the mentorship of Professor Margaret McFall-Ngai, UW-Madison Department of Medical Microbiology & Immunology. Amani’s characterization of a gene and protein found in a small tropical squid resulted in her first scientific publication and poster presentation.
Fast forward— after receiving a B.S. in Biomedical Engineering at Michigan Technological University (which included working in a tissue engineering lab and two summers interning at Promega Corporation under the supervision of Dr. Dan Lazar to help develop an assay for autophagy), Amani is now back in Madison. She is in her second year of graduate school and, working with Dr. Melissa Skala at the Morgridge Institute for Research, is currently mentoring Biotechnology YA Ava VanDommelen (senior from DeForest High School). Following in Amani’s footsteps, Ava will present her research nationally this January at the SPIE conference (the International Society of Optics and Photonics). Continue reading “Playing it Forward: Biotechnology Youth Apprenticeship and Mentorship”
Dr. Walter Blum wins trip to Promega headquarters as part of Promega Switzerland’s 25th Anniversary celebration.
Walter Blum knew how normal cells worked. He had studied and read about the pathways that regulated cell cycles, growth and development; he saw the cell as an amazingly well programmed, intricate machine. What he wanted to understand was: “Why does a cell become crazy? How does it escape immune system surveillance?”
Last week I had the opportunity to sit down with Dr. Blum, a customer of our Promega Switzerland branch. Dr. Blum won a trip to visit our campus in Madison for a week as part of an anniversary celebration for our Switzerland branch. While here, he got an inside peek at research and manufacturing operations, chatted with our scientists, met with our marketing teams and saw the sights in Madison. We talked about his work and what he learned and is taking back with him from his trip to Madison. Continue reading “Genes to Cells to Genomes: Where Will Your Research Questions Take You?”
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