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Chemical and Life Science Engineering Professor Michael “Pete” Peters, Ph.D., is investigating more efficient ways to manufacture biologic pharmaceuticals using a radial flow bioreactor he developed. With applications in vaccines and other personalized therapeutic treatments, biologics are versatile. Their genetic base can be manipulated to create a variety of effects from fighting infections by stimulating an immune response to weight loss by producing a specific hormone in the body. Ozempic, Wegovy and Victoza are some of the brand names for Glucagon-Like Peptide-1 (GLP-1) receptor agonists used to treat diabetes. These drugs mimic the GLP-1 peptide, a hormone naturally produced in the body that regulates appetite, hunger and blood sugar. “I have a lot of experience with helical peptides like GLP-1 from my work with COVID therapeutics,” says Peters. “When it was discovered that these biologic pharmaceuticals can help with weight loss, demand spiked. These drug types were designed for people with type-2 diabetes and those diabetic patients couldn’t get their GLP-1 treatments. We wanted to find a way for manufacturers to scale up production to meet demand, especially now that further study of GLP-1 has revealed other applications for the drug, like smoking cessation.” Continuous Manufacturing of Biologic Pharmaceuticals Pharmaceuticals come in two basic forms: small-molecule and biologic. Small-molecule medicines are synthetically produced via chemical reactions while biologics are produced from microorganisms. Both types of medications are traditionally produced in a batch process, where base materials are fed into a staged system that produces “batches” of the small-molecule or biologic medication. This process is similar to a chef baking a single cake. Once these materials are exhausted, the batch is complete and the entire system needs to be reset before the next batch begins. “ The batch process can be cumbersome,” says Peters. “Shutting the whole process down and starting it up costs time and money. And if you want a second batch, you have to go through the entire process again after sterilization. Scaling the manufacturing process up is another problem because doubling the system size doesn’t equate to doubling the product. In engineering, that’s called nonlinear phenomena.” Continuous manufacturing improves efficiency and scalability by creating a system where production is ongoing over time rather than staged. These manufacturing techniques can lead to “end-to-end” continuous manufacturing, which is ideal for producing high-demand biologic pharmaceuticals like Ozempic, Wegovy and Victoza. Virginia Commonwealth University’s Medicines for All Institute is also focused on these production innovations. Peters’ continuous manufacturing system for biologics is called a radial flow bioreactor. A disk containing the microorganisms used for production sits on a fixture with a tube coming up through the center of the disk. As the transport fluid comes up the tube, the laminar flow created by its exiting the tube spreads it evenly and continuously over the disk. The interaction between the transport medium coming up the tube and the microorganisms on the disk creates the biological pharmaceutical, which is then taken away by the flow of the transport medium for continuous collection. Flowing the transport medium liquid over a disc coated with biologic-producing microorganisms allows the radial flow bioreactor to continuously produce biologic pharmaceuticals. “There are many advantages to a radial flow bioreactor,” says Peters. “It takes minutes to switch out the disk with the biologic-producing microorganisms. While continuously producing your biologic pharmaceutical, a manufacturer could have another disk in an incubator. Once the microorganisms in the incubator have grown to completely cover the disk, flow of the transport medium liquid to the radial flow bioreactor is shut off. The disk is replaced and then the transport medium flow resumes. That’s minutes for a production changeover instead of the many hours it takes to reset a system in the batch flow process.” The Building Blocks of Biologic Pharmaceuticals Biologic pharmaceuticals are natural molecules created by genetically manipulating microorganisms, like bacteria or mammalian cells. The technology involves designing and inserting a DNA plasmid that carries genetic instructions to the cells. This genetic code is a nucleotide sequence used by the cell to create proteins capable of performing a diverse range of functions within the body. Like musical notes, each nucleotide represents specific genetic information. The arrangement of these sequences, like notes in a song, changes what the cell is instructed to do. In the same way notes can be arranged to create different musical compositions, nucleotide sequences can completely alter a cell’s behavior. Microorganisms transcribe the inserted DNA into a much smaller, mRNA coded molecule. Then the mRNA molecule has its nucleotide code translated into a chain of amino acids, forming a polypeptide that eventually folds into a protein that can act within the body. “One of the disadvantages of biologic design is the wide range of molecular conformations biological molecules can adopt,” says Peters. “Small-molecule medications, on the other hand, are typically more rigid, but difficult to design via first-principle engineering methods. A lot of my focus has been on helical peptides, like GLP-1, that are a programmable biologic pharmaceutical designed from first principles and have the stability of a small-molecule.” The stability Peters describes comes from the helical peptide’s structure, an alpha helix where the amino acid chain coils into a spiral that twists clockwise. Hydrogen bonds that occur between the peptide’s backbone creates a repeating pattern that pulls the helix tightly together to resist conformational changes. “It’s why we used it in our COVID therapeutic and makes it an excellent candidate for GLP-1 continuous production because of its relative stability,” says Peters. Programming The Cell Chemical and Life Science Engineering Assistant Professor Leah Spangler, Ph.D., is an expert at instructing cells to make specific things. Her material science background employs proteins to build or manipulate products not found in nature, like purifying rare-earth elements for use in electronics. “My lab’s function is to make proteins every day,” says Spangler. “The kind of proteins we make depends entirely on the project they are for. More specifically I use proteins to make things that don’t occur in nature. The reason proteins don’t build things like solar cells or the quantum dots used in LCD TVs is because nature is not going to evolve a solar cell or a display surface. Nature doesn’t know what either of those things are. However, proteins can be instructed to build these items, if we code them to.” Spangler is collaborating with Peters in the development of his radial flow bioreactor, specifically to engineer a microorganismal bacteria cell capable of continuously producing biologic pharmaceuticals. “We build proteins by leveraging bacteria to make them for us,” says Spangler. “It’s a well known technology. For this project, we’re hypothesizing that Escherichia coli (E. coli) can be modified to make GLP-1. Personally, I like working with E. coli because it’s a simple bacteria that has been thoroughly studied, so there’s lots of tools available for working with it compared to other cell types.” Development of the process and technique to use E. coli with the radial flow bioreactor is ongoing. “Working with Dr. Spangler has been a game changer for me,” says Peters. “She came to the College of Engineering with a background in protein engineering and an expertise with bacteria. Most of my work was in mammalian cells, so it’s been a great collaboration. We’ve been able to work together and develop this bioreactor to produce GLP-1.” Other Radial Flow Bioreactor Applications Similar to how the GLP-1 peptide has found applications beyond diabetes treatment, the radial flow bioreactor can also be used in different roles. Peters is currently exploring the reactor’s viability for harnessing solar energy. “One of the things we’ve done with the internal disc is to use it as a solar panel,” says Peters. “The disk can be a black body that absorbs light and gets warm. If you run water through the system, water also absorbs the radiation’s energy. The radial flow pattern automatically optimizes energy driving forces with fluid residence time. That makes for a very effective solar heating system. This heating system is a simple proof of concept. Our next step is to determine a method that harnesses solar radiation to create electricity in a continuous manner.” The radial flow bioreactor can also be implemented for environmental cleanup. With a disk tailored for water filtration, desalination or bioremediation, untreated water can be pushed through the system until it reaches a satisfactory level of purification. “The continuous bioreactor design is based on first principles of engineering that our students are learning through their undergraduate education,” says Peters. “The nonlinear scaling laws and performance predictions are fundamentally based. In this day of continued emphasis on empirical AI algorithms, the diminishing understanding of fundamental physics, chemistry, biology and mathematics that underlie engineering principles is a challenge. It’s important we not let first-principles and fundamental understanding be degraded from our educational mission, and projects like the radial flow bioreactor help students see these important fundamentals in action.”
Global audience in Copenhagen, Denmark, will learn of Gene Editing Institute research targeting the NRF2 gene in cancer cells Kelly Banas, Ph.D., principal investigator at ChristianaCare’s Gene Editing Institute, will present her latest research discovery related to targeting the NRF2 gene in cancer cells at the first CRISPR Medicine Conference held in Copenhagen, Denmark, April 22 to 25. The Gene Editing Institute’s research has focused on the NRF2 gene and the strong immune response it causes within cancer cells, allowing them to grow resistant to chemotherapy and leading cancer treatments to fail. By disrupting the NRF2 gene in cancer cells while allowing healthy cells to continue producing it, chemotherapy treatment becomes more effective. Gene Editing Institute principal investigators Kelly Banas, Ph.D., and Natalia Rivera-Torres, Ph.D., in the lab. Banas’ latest research delves into the mechanism of DNA repair following the removal of NRF2, ensuring that surrounding DNA in healthy cells is not affected and that the repair does not produce an unexpected outcome. “I’m extremely honored to be invited to this conference to highlight the work that all of our researchers at the Gene Editing Institute have put into this study,” Banas said. “The work we have done to characterize the impact of CRISPR on the NRF2 gene has changed how we approach new cancer targets. “This has influenced how we design experiments and analyze our data,” she said, “so it’s got a big impact on not just our work, but the work of anyone we collaborate with in the future. This community is full of phenomenal voices, and we’re committed to sharing our work in contexts like this to continue building a foundation of CRISPR research that will uplift treatment for some of the deadliest and most resilient cancers and diseases.” Read about Banas’ earlier research here.
Frequent tanning can signal excessive concern over image and vulnerability to taking health risks, researcher says Getty Images People who often sunbathe or use tanning beds are more likely to try risky weight-loss methods and have cosmetic surgery, as well as get tattoos and piercings. But while people who seldom tan also may try unsafe diets and cosmetic surgery, they rarely opt for tattoos or piercings, according to a Baylor University study. "When compared to infrequent tanners, frequent body-tanners — regardless of whether they are tanned by ultraviolet light from the sun, ultraviolet light from a tanning bed or methods such as tanning sprays that do not involve UV light — showed significantly higher behavioral intentions to engage in risky appearance-related behaviors overall," said Jay Yoo, Ph.D., associate professor of family and consumer sciences in Baylor's Robbins College of Health and Human Sciences. "Safer tanners, on the other hand, are more concerned about modifying their bodies in ways such as tattoos and piercing that may carry a stigma," Yoo said. Most skin cancer prevention campaigns have emphasized avoidance of getting sunburned, reducing UV exposure and applying sunscreen, but they have neglected the individual's experience with social and appearance concerns, he said. But "Excessive tanning can serve as a possible sign of overt concern over body image, with vulnerability to greater health risks," Yoo said. His research article — "A Study of the Relationships between Tanning Methods and the Intention to Engage in Risky Appearance-Related Behaviors" — is published in Family and Consumer Sciences Research Journal. Data for the study was collected from an online survey of 395 female college students in the southern United States. The major contributor to skin cancer is frequent exposure to ultraviolet rays, with skin cancer the most common — and one of the most preventable — types of cancer, according to the American Cancer Society. Ironically, previous research has found that many people choose to tan because they believe a tan makes them look thinner and more fit, Yoo said. Tanning has gone in and out of fashion, Yoo noted. Tans at one time were associated with lower classes who worked outdoors — in contrast with the Southern belles of more than a century ago, who used parasols to protect their skin and to look pale and refined. In the 1920s, fashion designer Coco Chanel started a fad after accidentally getting sunburned while visiting the French Riviera, Yoo said. Tanning remained popular, with high-fashion models often sporting tans, whether from UV exposure or sprays and bronzers. And these days, some people sport tattoos along with their tans, he said. The study found that: Frequent tanners who expose themselves to UV rays through sunbathing or tanning beds have the strongest intentions to engage in a wider range of risky appearance-related behaviors when compared to infrequent tanners or spray tanners. Such behaviors include extreme weight control methods, such as diet pills, self-induced vomiting, laxatives and diuretics; cosmetic surgery and Botox injections; spa treatments, such as hair removal by waxing (which has been associated with rashes and infections) and gel nail polish (done with UV curing and associated with DNA damage to the skin that can result in premature aging and possibly cancer; and tattoos or piercings. Infrequent tanners, as well as "safe" tanners who seek to achieve an ideal tan without ultraviolet methods (sprays, lotions or bronzers) are much less likely to engage in behaviors that may convey certain stereotypes, such as tattoos or piercings with visual symbols or messages. But they are willing to try other risky appearance-related behaviors. Yoo suggested that intervention strategies adapted for healthcare providers to reduce UV exposure and skin cancer could use stigmatization — perhaps through images of tattooed or pierced individuals who also are tanned. "A negative stigma attached to UV exposure can create ambivalence in our society about achieving a tanned appearance," Yoo said. "This could decrease the popularity of tanning in much the same way the negative stereotyping of smoking and education about its health risks have reduced the number of people who smoke." He noted that in the 1940s and 1950s, smoking was idealized, especially in Hollywood movies, but "there has been a cultural shift," he said. "One way to change the appeal of tanning would be to make it un-cool," Yoo said. "If I tan and people look at me funny, I'm not going to tan anymore." While another way to stigmatize tanning would be to stress the health consequences, "for young people it may be more effective to emphasize the appearance," Yoo said. "The tanning that makes me attractive now may be counteracted for the long haul because at 50 or 60, I may have leathery skin. "Given that tanning emerged as a fashion trend, gradual attitudes toward dangerous tanning can be made possible in a similar fashion," he said.
Amanda Hewes, MS, education program manager at ChristianaCare’s Gene Editing Institute, has been named one of the 2023 Outstanding Delaware Women in STEM by Million Women Mentors, an international movement dedicated to encouraging girls and women to pursue careers in science, technology, engineering and math (STEM). Hewes’ selection spotlights her dedication to engaging young people in the science of gene editing by introducing the Gene Editing Institute’s CRISPR in a BoxTM educational toolkit into classrooms across Delaware and her commitment to bridging disparities in STEM education. “I’m overjoyed to be honored among so many amazing women in this state,” Hewes said. “It’s humbling to be considered and to stand alongside them. All of these women foster and lead dynamic communities of young women that inspire me every day. I hope that I can do the same by making young women in this state feel empowered through the work that I do.” Hewes joined ChristianaCare’s Gene Editing Institute in 2017 with a focus on expanding its CRISPR gene editing system in a cell-free environment. She was first author in a publication in Nature that established the highly innovative “gene editing on a chip” protocol that allowed CRISPR to edit DNA outside of the cell for the first time. This methodology enables researchers to take fragments of DNA extracted from human cells, place them in a test tube and precisely engineer multiple changes to the genetic code. This gene editing system eventually led to the creation of the CRISPR in a Box™ toolkit. This innovative educational resource provides a way for students to learn about this exciting frontier of science through a hands-on exercise in which they use CRISPR gene editing to disrupt a synthetic gene within a plasmid. The simplicity of this experiment allowed for the reaction to be developed into a remarkable teaching tool that can be brought into most school laboratories containing basic laboratory equipment. Once CRISPR in a Box™ was developed, Hewes recognized the potential it could have for high school and college students. She took on a new role as education program manager and expanded the Gene Editing 360™ platform, which is the Gene Editing Institute’s suite of educational tools for engaging students and the public. “Amanda has set us on a tremendous path toward providing more educational opportunities for Delaware students,” said Eric Kmiec, Ph.D., director of ChristianaCare’s Gene Editing Institute. “She’s inspired young women in multiple states and has created so much of this program with her own ingenuity and passion.” Hewes was honored alongside 10 other women by Gov. John Carney, Lt. Gov. Bethany Hall-Long and others at the Delaware State House with the signing of a proclamation to declare March 24, 2023, as “Delaware Women and Girls in STEM Day.”
Gene Editing Institute Opens a Unique Learning Lab for High School and College Students
Free program uses CRISPR in a Box™ toolkit to teach the power of gene editing To inspire the next generation of students to pursue careers in STEM (science, technology, engineering and math) and learn about the power of genomic science, ChristianaCare’s Gene Editing Institute has launched a new Learning Lab on its premises that offers educational programming about revolutionary CRISPR gene editing technology. Located next to the Gene Editing Institute’s lab on the University of Delaware’s STAR Campus, the Learning Lab is a physical space that provides an immersive field trip experience for upper-level high school students and college undergraduates who may not have access at their schools to a laboratory to conduct gene editing experiments. There is no cost for schools to use the lab or for the materials to conduct the experiment. The Gene Editing Institute wants to ensure that all schools have equal opportunity to participate in educational programming at the lab. Students using the lab can perform a gene editing experiment in a single day using the Gene Editing Institute’s innovative CRISPR in a Box™ educational toolkit. All materials in the kit are safe, synthetic materials, and allow students to perform CRISPR gene editing with non-infectious E. coli bacteria. They will be able to see an appearance change indicating gene editing has occurred at the end of their experiment. “Students around the country, no matter where they go to school, have the potential to be scientists, researchers and laboratory technicians,” said Eric Kmiec, Ph.D., executive director and chief scientific officer of ChristianaCare’s Gene Editing Institute. “Our hope is that by creating access and space for students to explore, we can inspire the next generation of students to pursue STEM careers. The Learning Lab allows us to help cultivate the next generation of genetic scientists and strengthen Delaware and our region as a leader in biotechnology.” Education Program Manager Amanda Hewes, MS, developed the Learning Lab after noticing a problem that was undercutting the opportunities of teachers to bring gene editing experiments into the classroom — a lack of space and equipment. Amanda Hewes, education program coordinator, assists students from Wilmington Charter School with their samples of DNA during a Learning Lab experiment. “We don’t want anything to hinder the way students learn about CRISPR gene editing,” Hewes said. “If a student feels like there are too many steps, or a teacher doesn’t have an essential piece of equipment, then we’ve lost an opportunity to bring the next generation of scientists into the lab. We’re striving to break down as many barriers as possible for students.” Learning real-world applications of gene editing The Learning Lab also allows students to speak directly with experts in the field about careers in biotechnology and gene editing as they learn the difference between such things as phenotypic and genotypic readouts in their gene editing experiments. This gives students the chance to ask about the real-world application of genome experiments in a research lab. It also lets them think about their place in a lab setting. “I’ve never been in an actual lab setting before,” said Shiloh Lee, a junior at the Charter School of Wilmington, at a recent class. “I think it is very, very cool to be able to experience it.” “I’ve learned a lot of new skills with the micropipetting,” said Pauline Zhuang, a senior at The Charter School of Wilmington. “We don’t have the same resources at our school. The CRISPR in a Box is such a great resource. My classmates and I have been able to experience, firsthand, what it is like to actually do gene editing.” Through the program, the Gene Editing Institute hopes to educate 1,000 students by spring 2024. Currently, the lab is on track to engage more than 200 students by the end of the spring 2023 semester. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are the hallmark of a bacterial defense system that forms the basis for CRISPR-Cas 9 genome editing technology. The CRISPR technology enables researchers to modify genes in living cells and organisms and may make it possible to correct mutations at precise locations in the human genome in order to treat genetic causes of disease. For more information about the Learning Lab and the educational program, email geneeditinginstitute@christianacare.org.
Discovery may lead to more precise treatments for advanced colorectal cancer Researchers at ChristianaCare’s Cawley Center for Translational Cancer Research at the Helen F. Graham Cancer Center & Research Institute have demonstrated for the first time that microRNA (miRNA) expression leads to a diversity of cancer stem cells within a colorectal cancer tumor. This diversity of cancer cells may explain why advanced colorectal cancer is difficult to treat. Study results have been in the Journal of Stem Cell Research and Therapy. The findings broaden the understanding of how miRNA expression adds to cancer stem cell diversity and may lead to more precise anti-cancer treatments for patients with advanced colorectal cancer. The research builds on prior discoveries by scientists at the Graham Cancer Center about how cancer stem cell activity contributes to the development and spread of colorectal cancer. “Our research shows — at least in the laboratory — that there are different subpopulations of cancer stem cells in a tumor, and they may be driving the growth of the cancer,” said Principal Investigator Bruce Boman, M.D., Ph.D., MSPH, FACP, medical director of Cancer Genetics and Stem Cell Biology at the Graham Cancer Center. “In one subpopulation of cancer stem cells, its miRNA will shut down the stem cell genes that are expressed in another subpopulation, and vice versa, within the same tumor.” From left: ChristianaCare researchers Lynn Opdenaker, Ph.D., Brian Osmond, Bruce Boman, M.D., Ph.D., Chi Zhang, Victoria Hunsu, Caroline Facey, Ph.D. Not pictured Victoria Stark, MS. The study focused on the composition of cancer stem cells within a colorectal cancer cell line (HT29) in the laboratory setting. Researchers evaluated the different cancer stem cell subpopulations that were identified by examining patterns of miRNA expression in each subpopulation and looking for differences. The researchers found that each of the four diverse subpopulations that were studied (ALDH, LRIG1, CD166 and LGR5) had a different miRNA expression or gene signature. The researchers found that miRNA expression could inhibit the expression of messenger RNA (mRNA), which carries instructions from the DNA to encode specific proteins within cells. Therefore, miRNA, by controlling gene expression, dictate which proteins are contained in the stem cells. The researchers discovered the miRNA that are upregulated in certain cancer stem cell subpopulations are downregulated in other cancer stem cell subpopulations. In this way, differential miRNA expression leads to cancer stem cell heterogeneity within colorectal tumor tissue. “It’s an early research finding and needs to be followed up with other experiments, but it has clear relevance to the clinic,” Boman said. “The question is: Can you target the miRNA to make cancer more sensitive to certain treatments? Because we know what the current anti-cancer treatments are targeting, we may be able to modulate or manipulate the cancer, so it becomes more sensitive to the treatment.” Identification of a network of genes regulated by microRNAs in a cancer stem cell subpopulation. For more than a decade, ChristianaCare’s researchers have contributed to the understanding of the role that cancer stem cells and miRNA expression play in the development and spread of colorectal cancer. This latest finding builds on earlier discoveries that examined a link between two cellular signaling pathways: retinoic acid (RA) signaling and wingless-related integration site (WNT) signaling, which are dysregulated by different gene mutations in colorectal tumors. The RA signaling pathway induces growth arrest and differentiation of cancer stem cells. Notably, retinoic acid is effective against other types of cancer such as leukemia. The role of the WNT signaling pathway has an opposite effect on tumor growth. The WNT signaling pathway is activated by a mutation in the APC (adenomatous polyposis coli) gene in about 90% of cases of colorectal cancer. In APC mutant tissue, dysregulated miRNA expression may underlie an imbalance between the RA and WNT signaling, which then leads to intratumoral cancer stem cell heterogeneity. Still, this mechanism that may enable the cancer to proliferate could also provide clues on how to more effectively treat cancer. “If you’ve got an imbalance between these two signaling pathways, then you’ve likely got a growth driver,” Boman said. “The question is: Can you suppress the WNT signaling and enhance the retinoic acid signaling?” It may be possible to increase the sensitivity of colorectal cancer to retinoic acid-type drugs, and therapeutically shift the balance between different cancer stem cell subpopulations, thereby suppressing cancer growth. More research is needed to determine how targeted cancer therapies containing retinoic acid-type drugs may be made more effective against advanced cancer. This research will be presented at the annual meeting of the American Association for Cancer Research in Orlando, Florida, April 14-19. This research project was supported by a grant from the Lisa Dean Moseley Foundation.
Protein engineer to explore route from DNA blueprint to synthetic antibodies – public lecture
Professor Anna Hine will explore how advances in protein engineering have enabled us to make both synthetic antibodies and their replacements Inaugural lecture will take place at Aston University on Tuesday 28 March 2023 at 6.30pm Members of the public may attend in person or online. Professor Anna Hine, a molecular biologist specialising in protein engineering in the College of Health and Life Sciences at Aston University, is to present her inaugural public lecture on Tuesday 28 March 2023. During her lecture, A route to synthetic antibodies (and their replacements), Professor Hine will take the audience from the basics of molecular biology to explaining her inventions in protein engineering, through to examining the ways in which her research is being applied internationally to develop synthetic antibodies. Professor Hine gained her PhD in molecular biology from The University of Manchester Institute of Science and Technology in 1992 and did her postdoctoral training at Harvard Medical School. She returned to the UK to take up a lectureship in molecular biology at Aston University in 1995. Professor Anna Hine, professor of protein engineering, said: “Antibodies are one of our major lines of defence against infection and we can create them very quickly to help incapacitate a multitude of biological invaders. Humans do this by changing the part of the antibody that recognises the invading pathogen, through a process of rapid, natural mutation. Protein engineers have learned to mimic this process in the laboratory to create synthetic proteins – particularly antibodies - for use in both therapy and fundamental research.” “I am delighted to have the opportunity to present our discoveries in a way that I hope will make just as much sense to non-scientists as to a scientific audience.” Similar to the natural mutation of antibodies, protein engineers can make vast numbers of tiny variations of a protein such as an antibody. Professor Hine added: “We will contemplate the vast numbers involved in protein engineering and present how our Aston University-based inventions have made the creation of DNA (and thus protein) ‘libraries’ as efficient as possible. “We will then examine the ensuing problem of how to find the few proteins that we really want from within a protein library. This includes collaborating with experts who specialise in computer-assisted library design and also working with those who have developed the latest methods to search the libraries that we make.” Professor Hine will also show how her latest collaborative projects are starting to move beyond the antibody itself. The lecture will take place at Aston University at 6.00pm for 6.30pm on Tuesday 28 March 2023. It will be followed by a drinks reception from 7.30 pm to 8.00 pm. The lecture is open to the public and free to attend. Places must be booked in advance via Eventbrite.
New research suggests model organisms may have evolved too far
A research team from Aston University and the Universities of Birmingham and Nottingham suggest model organisms evolved over 100 years may no longer be fit for purpose They found the bacterial strain Escherichia coli K-12 has been repeatedly cultured and mutated, resulting in many genetic changes The study has just been published in Microbial Genomics A research team from Aston University has found that the model organism used in laboratories for the past 100 years has evolved so extensively that it may no longer be fit for purpose. According to a new study, published in Microbial Genomics, the bacterial strain Escherichia coli K-12 has been repeatedly cultured and mutated, resulting in an organism that carries many genetic changes compared to the original isolated bacteria. The research team, from Aston University, and the Universities of Birmingham and Nottingham, made their discovery after re-examining the early preserved samples and looking at the base sequence of their DNA. They found a large number of differences at the DNA sequence level, and the differences are bigger when they examined currently used stocks that derived from the original samples. The work underscores the dangers of using one strain as a sole model. It also confirms that bacterial sequences evolve over short time scales and provides a fascinating insight into the first baby steps of molecular microbiology. Lead author Dr Doug Browning, of the School of Biosciences at Aston University, said: “The past 10 years have seen a massive amount of bacterial genome sequencing and the picture that is emerging is that bacterial genomes change very fast. This was unimaginable 100 years ago, and, of course, this is why folk back then were quick to adopt the K-12 strain as the model for everything.” The strain of bacteria in the study was originally isolated in 1922 from the faeces of a recuperating diptheria patient at Stanford University, in California. The strain was preserved and over time it, and many derivatives, were distributed to research laboratories around the world for use by researchers looking to understand the workings of living cells at the molecular level. While the number of genetic variations which have appeared in the intervening decades may sound alarm bells in some research areas, for others it may represent new research opportunities. Co-author Steve Busby, of the Institute of Microbiology and Infection at the University of Birmingham, said: “Actually the diversity that all this generates can add a new dimension to our understanding. It’s often true that things are seldom as they seem, and particularly so if you only study one strain.”
The CRISPR Dilemma: A Road To Saving Lives Riddled with Roadblocks
The New York Times recently published an Op-Ed by Dr. Fyodor Urnov unpacking the incredible advancement and possibilities of CRISPR gene editing technology on human lives. It also addressed some of the roadblocks and challenges preventing this "not so new" technology from getting to the finish line of promise. Dr. Eric Kmiec, the director of ChristianaCare's Gene Editing Institute, whose unparalleled research has led to over 18 patents that have advanced medical research, also shared his concern in a follow-up letter published by the New York Times about the many roadblocks standing in the way of life-saving opportunities with gene editing and CRISPR technology. Dr. Kmiec (above) in the lab "If we were able to safely and effectively approve a COVID vaccine in a year, we must do the same by pooling public and private funds and seek ways to speed science. Why can’t we support the most promising solutions to some of the longest running and most intractable of cancers or rare diseases?" The advancement of gene editing has not only been stalled by the outdated processes of medical reviews and policies, but many have introduced political and religious barriers. The idea of "playing God" or even Dr. Frankenstein when people hear the term "gene editing" raises ethical questions based on a lack of understanding. Some of these concerns are shared in this recent article in Futurism. Ask one of the 100 people afflicted with a gene defect that could cost them their lives at age 7 and the perspective may be a little different. Nature makes mistakes, often imperfect, and impacted by the ever-changing landscape, impacted by external factors that are either known or unknown. Gene editing, simply put, can fix typos in genes that have experienced a glitch. As Dr. Kmiec puts it, "It allows us to correct mutations that are inbred in the genome, it's correcting nature's mistakes — and nature does make a bunch of mistakes." Whether gene editing fits into a belief system or is too otherworldly for some to grapple with, Dr. Kmiec asserts that speeding up the delays put onto science by process, politics or fear will result in saving lives, saving pain and advancing possibility. Dr. Urnov agrees, "Scientists owe them and their families honesty about the chasm between a test tube in a lab and an IV line in a hospital. The greatest obstacles are not technical but legal, financial and organizational." Gene editing is a pioneering technology that can help humans, plants and animals alike. When it comes to putting it into action, at the very least, if science is there to help, everyone should have the choice to use it.
Winner of the 2022 Rosalind Franklin Essay Prize announced
Aston Medical School students compete for prestigious prize in essay writing competition Prize launched in honour of the renowned chemist, Rosalind Franklin This year’s theme is ‘Are there limits to freedom of expression in a medical school?’ The winner of this year’s Aston Medical School Rosalind Franklin Essay Prize has been announced as Shoheb Hassan, a 3rd year medical student. The annual essay writing competition is held in memory of the pioneering chemist Rosalind Franklin who was a chemist and X-ray crystallographer. Rosalind’s work was central to the understanding of the molecular structures of DNA: RNA, viruses, coal and graphite. The theme of this year’s competition was ‘Are there limits to freedom of expression in a medical school?’ The essays submitted were a reflective and personal perspective on freedom of expression within a medical school. This year’s winner Shoheb Hassan said: “I am so pleased and honoured to be awarded first prize. I sincerely enjoyed reflecting on the topic about freedom of expression in a medical school. I express my gratitude to Dr Daniel Franklin for this opportunity and I hope that upcoming students will benefit from their reflections just as much as I did.” Aston Medical School's Rosalind Franklin Essay Prize was conceived and funded by Dr Daniel Franklin in 2020. Daniel is a nephew of Rosalind Franklin and an alumnus of Aston University, graduating twice: once in 1981 with a PhD and again in 2013, when he was awarded an honorary degree. The judging panel included Daniel and staff from Aston Medical School. Daniel, who has been executive editor of The Economist since 2003, said: "Once again, the quality of the essays produced by Aston Medical School students was truly impressive and reflects their ability to reflect deeply and imaginatively about matters of medical education." The winning essay receives a prize of £750 and the runner up is awarded £250. For more information about Aston Medical School please visit our website.