As human lifespans have gotten longer, certain proteins in our bodies are increasingly prone to take on alternative shapes. These misfolded proteins can ultimately trigger neurodegenerative diseases such as Alzheimers, Parkinsons and Lou Gehrigs disease, formally known as amyotrophic lateral sclerosis (ALS).
Meredith Jackrel, assistant professor of chemistry in Arts & Sciences at Washington University in St. Louis, and her lab group study protein misfolding disorders. They are especially interested in how protein misfolding occurs, how it leads to disease and how scientists might be able to prevent or even reverse protein misfolding. Their work promises applications in flu vaccines as well as in the current coronavirus pandemic.
In this Q&A, Jackrel describes how her labs expertise in protein misfolding and neurodegenerative diseases has made them uniquely qualified to work on developing new amyloid-inspired vaccine technologies aimed at elderly populations.
How does your research relate to the current pandemic?
We are working on the development of new vaccine technologies specifically tailored to elderly populations. We originally initiated this project to evaluate new flu vaccine technologies, but this approach could also be relevant to COVID-19 since seniors are particularly susceptible to its severe complications.
A general problem with vaccination of elderly individuals is immuosenescence, or age-related dysfunction of the immune system. Immunosenescence is typically overcome by the addition of adjuvants to improve immune response and efficacy. However, adjuvants create local inflammation, which obstructs the immune system and makes vaccines less effective.
A colleague at WashU in biomedical engineering, Jai Rudra, studies self-assembling peptides as materials for developing novel vaccines that do not require the use of adjuvants. These self-adjuvanting peptide nanofibers are hypothesized to trigger the autophagy pathway, a kind of cellular recycling that can also promote good immunological functions, which has emerged as a potential vaccine target. Administration of these peptide nanofibers leads to robust, high-affinity, and neutralizing antibody responses without local reactions, making them attractive for vaccine delivery in the elderly.
To further pursue application of these nanofibers, we must now investigate the toxicity and clearance mechanism of these materials.
How are you using your expertise in protein folding/misfolding in your work on vaccine technology?
Peptide nanofiber materials rapidly assemble into configurations that closely resemble the underlying causes of neurodegenerative disorders. These amyloids are recognized as clumps of proteins that accumulate in patients with Alzheimers, Huntingtons and Parkinsons disease.
While there are key differences that we anticipate will not make use of these materials problematic, it is nonetheless essential that the safety and clearance mechanism of the peptide nanofiber vaccines be thoroughly tested. My labs expertise in the development of model systems to study the toxicity and mechanism of disease-associated amyloid proteins is therefore highly relevant to this project.
Furthermore, due to the complexities of studying the peptide nanofibers in mammalian cells, my labs expertise in the use of Bakers yeast as a model system is proving highly relevant for studying the mechanism of clearance of these new materials.
What are your specific goals in this project?
The primary goals for my lab are to determine the toxicity and mechanism of clearance of the peptide nanofiber vaccines in a yeast model system. We aim to compare the toxicity of the nanofibers to the toxicity of disease-associated proteins. We will also employ autophagy-deficient yeast models to establish the mechanism of clearance of the nanofibers. The Rudra lab then aims to assess the efficacy of the nanofiber-based vaccines in aged mice.
Where does the project stand now? What are the next steps?
We have established a yeast model system of these peptide nanofibers and completed much of the preliminary work. Excitingly, we have confirmed that these peptide nanofibers are not toxic in yeast and have made some new insights into their mechanism of clearance. We aim to complete the early stage of this project shortly, and the Rudra lab has begun work in animal systems. Once we complete work with the nanofibers alone, we will begin to test conjugates to various vaccine targets, notably those that underpin COVID-19.
Read this article:
Building better vaccines for the elderly | The Source - Washington University in St. Louis Newsroom
- Protein folding - Wikipedia [Last Updated On: August 18th, 2024] [Originally Added On: September 11th, 2019]
- Protein Folding: The Good, the Bad, and the Ugly - Science ... [Last Updated On: August 18th, 2024] [Originally Added On: September 13th, 2019]
- Protein Folding - Chemistry LibreTexts [Last Updated On: August 18th, 2024] [Originally Added On: September 14th, 2019]
- Protein Structure and Folding [Last Updated On: August 18th, 2024] [Originally Added On: September 19th, 2019]
- Structural Biochemistry/Proteins/Protein Folding ... [Last Updated On: August 18th, 2024] [Originally Added On: September 28th, 2019]
- Proteopathy - Wikipedia [Last Updated On: August 18th, 2024] [Originally Added On: October 1st, 2019]
- Folding@home - Wikipedia [Last Updated On: August 18th, 2024] [Originally Added On: October 1st, 2019]
- Denaturation and Protein Folding | Introduction to Chemistry [Last Updated On: August 18th, 2024] [Originally Added On: October 4th, 2019]
- Protein Folding - Anfinsen's Experiment ~ Biology Exams 4 U [Last Updated On: August 18th, 2024] [Originally Added On: October 4th, 2019]
- Protein Structures: Primary, Secondary, Tertiary, Quaternary ... [Last Updated On: August 18th, 2024] [Originally Added On: October 4th, 2019]
- Protein Folding - an overview | ScienceDirect Topics [Last Updated On: August 18th, 2024] [Originally Added On: October 6th, 2019]
- Thermodynamics of spontaneous protein folding: role of ... [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- Molecular Biology 02: 'Thermodynamics of protein folding' [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- The Science Behind Foldit | Foldit [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- Diseases Folding@home [Last Updated On: August 18th, 2024] [Originally Added On: October 8th, 2019]
- DeepMind timeline: The history of the UK's pioneering AI firm - Techworld.com [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Geroscience and it's Impact on the Human Healthspan: A podcast with John Newman - GeriPal - A Geriatrics and Palliative Care Blog [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Yumanity Therapeutics Initiates Phase 1 Clinical Trial of Lead Candidate YTX-7739 for the Treatment of Parkinson's Disease | Small Molecules | News... [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Tenure-Track or Tenure-Eligible Position in the Laboratory of Chemical Physics job with National Institutes of Health | 28302 - Chemical &... [Last Updated On: August 18th, 2024] [Originally Added On: October 10th, 2019]
- Food for the soul: Traditional gyza makers and eaters in Utsunomiya try to keep the dumplings rolling - The Japan Times [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- UT molecular evolution professor named 2019 American Physical Society Fellow - UT The Daily Texan [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- 9 must-have Instant Pot accessories for healthy eating - CNET [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- Researchers Find Fish Wearing Natural 'Bullet-Proof Vest' to Thwart Piranhas in Amazon - News18 [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- Christopher Dobson: chemist whose work on proteins advanced research into neurodegenerative diseases - The BMJ [Last Updated On: August 18th, 2024] [Originally Added On: October 19th, 2019]
- Two years in the making, Pizza Hut tests a round pizza box - Fast Company [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Fava Is All About Balance - East Bay Express [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Amazon fish wears nature's 'bullet-proof vest' to thwart piranhas - Reuters [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- RNA Folding Insights Lead to New Therapeutics and Synthetic Biology Technologies - Technology Networks [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- The Hidden Inactive Ingredient: Biological Products in Recombinant Pharmaceuticals - P&T Community [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Insights into Parkinson's Onset May Lie in New Model of Cell Aging and Damage - Parkinson's News Today [Last Updated On: August 18th, 2024] [Originally Added On: October 23rd, 2019]
- Antibiotics with novel mechanism of action discovered - Drug Target Review [Last Updated On: August 18th, 2024] [Originally Added On: October 25th, 2019]
- The top AI lighthouse projects to watch in biopharma - FierceBiotech [Last Updated On: August 18th, 2024] [Originally Added On: October 25th, 2019]
- UCI vision scientist Krzysztof Palczewski elected to National Academy of Medicine - UCI News [Last Updated On: August 18th, 2024] [Originally Added On: October 26th, 2019]
- Rett Syndrome Tied to Altered Protein Levels in Brain in Early Study - Rett Syndrome News [Last Updated On: August 18th, 2024] [Originally Added On: October 26th, 2019]
- Bulls-Eye: Imaging Technology Could Confirm When a Drug Is Going to the Right Place - On Cancer - Memorial Sloan Kettering [Last Updated On: August 18th, 2024] [Originally Added On: October 26th, 2019]
- Discover: Science is often wrong and that's actually a really good thing - Sudbury.com [Last Updated On: August 18th, 2024] [Originally Added On: November 2nd, 2019]
- IBM vs. Google and the Race to Quantum Supremacy - Citizen Truth [Last Updated On: August 18th, 2024] [Originally Added On: November 7th, 2019]
- Microprotein ID'd Affecting Protein Folding and Cell Stress Linked to Diseases Like Huntington's, Study Finds - Huntington's Disease News [Last Updated On: August 18th, 2024] [Originally Added On: November 7th, 2019]
- IBM vs. Google and the race to quantum supremacy - Salon [Last Updated On: August 18th, 2024] [Originally Added On: November 11th, 2019]
- That Junk DNA Is Full of Information! - Advanced Science News [Last Updated On: August 18th, 2024] [Originally Added On: November 16th, 2019]
- Argonne Researchers to Share Scientific Computing Insights at SC19 - HPCwire [Last Updated On: August 18th, 2024] [Originally Added On: November 16th, 2019]
- How to Make the Most of Your Old Tech - New York Magazine [Last Updated On: August 18th, 2024] [Originally Added On: November 16th, 2019]
- 2 tricked-out pies to be thankful for: pear with cranberries and pumpkin with ginger praline - The Gazette [Last Updated On: August 18th, 2024] [Originally Added On: November 17th, 2019]
- From Mediterranean Lentil Salad to Cinnamon Raisin Bread: Our Top 10 Vegan Recipes of the Day! - One Green Planet [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- What is Biophysical Analysis? - The John Innes Centre [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- Thermodynamic probes of instability: application to therapeutic proteins - European Pharmaceutical Review [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- In science, its better to be curious than correct - The Conversation CA [Last Updated On: August 18th, 2024] [Originally Added On: November 22nd, 2019]
- New Study Reveals US Airlines With the Healthiest Food Options - TravelPulse [Last Updated On: August 18th, 2024] [Originally Added On: November 29th, 2019]
- Study Reveals Hepatitis A Originated in Insects - Advanced Science News [Last Updated On: August 18th, 2024] [Originally Added On: November 29th, 2019]
- How Home-Baked Bread Is Defying the Industrial Food System - YES! Magazine [Last Updated On: August 18th, 2024] [Originally Added On: November 29th, 2019]
- Black Friday Is Absolutely Massive. Here Are a Bunch of Deals We Couldn't Call Out Individually - Gear Patrol [Last Updated On: August 18th, 2024] [Originally Added On: November 30th, 2019]
- A conserved ATP- and Scc2/4-dependent activity for cohesin in tethering DNA molecules - Science Advances [Last Updated On: August 18th, 2024] [Originally Added On: November 30th, 2019]
- Ancient Worm Reveals Way to Destroy Toxic Cells Potential New Therapy for Huntingtons and Parkinsons - SciTechDaily [Last Updated On: August 18th, 2024] [Originally Added On: December 11th, 2019]
- Biologics Market Size Expand at a CAGR of 3.9 With $399.5 Billion By 2025 - MENAFN.COM [Last Updated On: August 18th, 2024] [Originally Added On: December 11th, 2019]
- Exploring the Diversity of Parkinson's Proteins - Technology Networks [Last Updated On: August 18th, 2024] [Originally Added On: December 11th, 2019]
- Early detection of brain degeneration on the horizon with innovative sensor - UNM Newsroom [Last Updated On: August 18th, 2024] [Originally Added On: December 16th, 2019]
- Holiday cookies from around the world | Features - yoursun.com [Last Updated On: August 18th, 2024] [Originally Added On: December 22nd, 2019]
- The Art of Origami is Now A Key Tool That Helps Doctors Save Lives - Nature World News [Last Updated On: August 18th, 2024] [Originally Added On: December 23rd, 2019]
- Nanopores can identify the amino acids in proteins, the first step to sequencing - University of Illinois News [Last Updated On: August 18th, 2024] [Originally Added On: December 23rd, 2019]
- Wow your New Year's Eve guests with a puff pastry appetizer - KARE11.com [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- The 10 most compelling product innovations of 2019 - Fast Company [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- Our best recipes from 2019 | Food and cooking - STLtoday.com [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- The best WIRED long reads of 2019 - Wired.co.uk [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- Structure of Drosophila melanogaster ARC1 reveals a repurposed molecule with characteristics of retroviral Gag - Science Advances [Last Updated On: August 18th, 2024] [Originally Added On: January 1st, 2020]
- Gocycle to partner with nutrition brand Fuel10k to promote benefits of e-bikes - Bike Biz [Last Updated On: August 18th, 2024] [Originally Added On: January 16th, 2020]
- The Importance of Understanding TargetProtein Interactions in Drug Discovery - Technology Networks [Last Updated On: August 18th, 2024] [Originally Added On: January 16th, 2020]
- How DeepMind is unlocking the secrets of dopamine and protein folding with AI - VentureBeat [Last Updated On: August 18th, 2024] [Originally Added On: January 16th, 2020]
- How To Grow (Almost) Anything - Hackaday [Last Updated On: August 18th, 2024] [Originally Added On: January 19th, 2020]
- U of T's Peter Wittek, who will be remembered at Feb. 3 event, on why the future is quantum - News@UofT [Last Updated On: August 18th, 2024] [Originally Added On: January 19th, 2020]
- The DeepMind algorithm to solve two complex problems of biology - The Times Hub [Last Updated On: August 18th, 2024] [Originally Added On: January 19th, 2020]
- High Focus on Product Innovation & Development to Assist the Growth of the Folding Cartons Market between and . 2017 2025 Dagoretti News -... [Last Updated On: August 18th, 2024] [Originally Added On: January 24th, 2020]
- Folded, frozen, and faster: JUST Egg is now more convenient, and cheaper, to enjoy - FoodNavigator-USA.com [Last Updated On: August 18th, 2024] [Originally Added On: January 24th, 2020]
- Phyllo, cheese, heaven: Balkan women have been making these treats for centuries - The Gazette [Last Updated On: August 18th, 2024] [Originally Added On: January 26th, 2020]
- Phyllo, cheese, heaven: Balkan women have been making these treats for centuries - Waterbury Republican American [Last Updated On: August 18th, 2024] [Originally Added On: January 28th, 2020]
- The keto diet: Its highs and lows plus 5 recipes - The Gazette [Last Updated On: August 18th, 2024] [Originally Added On: February 12th, 2020]
- Study Shows How Soap Molecules Alter the Protein Structure - AZoM [Last Updated On: August 18th, 2024] [Originally Added On: February 12th, 2020]
- CryoEM of CBD Tau Suggests Another Unique Protofibril - Alzforum [Last Updated On: August 18th, 2024] [Originally Added On: February 16th, 2020]
- Working In Science Was A Brutal Education. Thats Why I Left. - BuzzFeed News [Last Updated On: August 18th, 2024] [Originally Added On: February 17th, 2020]
- The Evolution of the Eye, Demystified - Discovery Institute [Last Updated On: August 18th, 2024] [Originally Added On: February 28th, 2020]
- L-serine could be used to treat ALS, after promising study results - Drug Target Review [Last Updated On: August 18th, 2024] [Originally Added On: February 28th, 2020]