NEWS
Meet Alex Kashkin: UT Student by Day, Local Austin Entrepreneur by Night
Posted on January 12, 2021
As the ongoing SARS-CoV-2 pandemic has led to a flurry of behind-the-scenes diagnostic research activity at UT Austin, one undergraduate and his ingenuity have been instrumental in their contributions to recent scientific developments at the University. Meet Alex Kashkin: founder of GeneTiger, a company that produces inexpensive, point-of-care genetic testing devices that can be operated by minimally-trained users to run various diagnostic assays. According to Alex, even children have been able to use the device correctly (without reading the instructions)! UT student by day, local Austin entrepreneur by night, Alex has been helping push forward the genetic testing industry…
Engineering βst DNA polymerase for Improved Sensitivity of LAMP Detection of SARS-CoV-2
Posted on November 12, 2020
As the coronavirus pandemic continues, many researchers have been using proven LAMP (loop-mediated isothermal amplification) assays to detect SARS-CoV-2 virions in patient samples. However, LAMP assays are known to frequently produce inaccurate DNA/RNA replicates that can skew results and trigger false positives. To this end, the Ellington Lab developed a variant of LAMP—termed LAMP-OSD (LAMP with Oligonucleotide Strand Displacement)—containing OSD probes that alert scientists to the presence of the improper replicates. These modified LAMP-OSD assays are extremely useful in low-resource and point-of-care situations and can even detect the virus in crude human saliva samples. However, the limited choice and supply of LAMP enzymes have resulted in higher costs for scientists using LAMP-OSD assays; to solve this roadblock, the Ellington Lab has demonstrated in their latest preprint that the utility of LAMP-OSD assays can be further improved by modifying the assays at a molecular level. By adding extra DNA- or RNA-binding domains to βst DNA polymerase (a strand-displacing DNA polymerase used in LAMP), researchers at the Ellington Lab have greatly improved the performance of these LAMP-OSD assays. More importantly, their procedure utilizes enzymes that were developed in the lab and can be easily created by any researcher, thus allowing more scientists to use LAMP-OSD assays at a lower cost.
EBRC Receives $87 Million Award for BioMADE
Posted on October 30, 2020
Last week, the Department of Defense announced an $87.5 million, seven-year award to the Bioindustrial Manufacturing and Design Ecosystem (BioMADE), a nonprofit created by the Engineering Biology Research Consortium (EBRC), for a new Manufacturing Innovation Institute (MII). BioMADE joins a system of eight other MIIs (the earliest of which was established by the DoD in 2012) as part of the Manufacturing USA network, an end-to-end ecosystem for domestic manufacturing to secure America’s future through manufacturing innovation, education, and collaboration. BioMADE will greatly accelerate the commercialization of biotechnology inventions originating from American R&D in universities, start-ups, and National Labs. Operating out of the University of Minnesota in St. Paul, BioMADE will collaborate with public and private entities to advance sustainable bioindustrial manufacturing technologies. We are happy to announce that the Ellington Lab, along with other UT Austin entities (the Davies Lab, the Barrick Lab, and the Contreras Lab), will be part of the BioMADE team for sustainable manufacturing.
New Paper Reveals Structure of Revolutionary Synthetic Reverse Transcriptase
Posted on September 21, 2020
Using directed evolution—a protein engineering method that mimics natural selection—a research team led by Dr. Andy Ellington and Jared Ellefson (Ansa Biotechnologies) has created a synthetic reverse transcriptase dubbed “reverse transcription xenopolymerase,” more commonly referred to as RTX. This enzyme catalyzes the formation of DNA from an RNA template (i.e. reverse transcription) and was evolved in vitro from the B-family DNA polymerase KOD. By conducting structural analyses of RTX in complex with either a DNA double-strand or an RNA-DNA hybrid double-strand, as well as comparing the crystal structures of RTX with the original KOD polymerase, researchers are gleaning new information on how to engineer and alter substrate specificity of enzymes. The RTX structures, as well as the team’s findings detailing the similarities between RTX and naturally occurring RNA-dependent DNA polymerases (e.g. telomerase and reverse transcriptase), are available here for additional reading.
Dr. Andy Ellington Speaks to University of Texas COVID-19 Modeling Consortium
Posted on September 14, 2020
Dr. Ellington also recently spoke to the UT COVID-19 Modeling Consortium, a regular topics group that is an outgrowth of the extraordinary work carried out by Dr. Lauren Meyers, who regularly models and predicts the epidemiology of the virus. Dr. Ellington emphasized the need for more public health-friendly tests, including de-identified, anonymous tests from saliva, and environmental tests of buildings and other environments. In this way, individuals and businesses could get the best view of their own public health situation, and make plans accordingly without having to rely upon medical or patient records, or even contact-tracing. The public health view of the epidemic is increasingly coming to the fore as efforts to control the virus via clinical management continue to be problematic.
Dr. Andy Ellington Speaks to the Engineering Biology Research Consortium (EBRC)
Posted on September 12, 2020
The Engineering Biology Research Consortium (EBRC) is a nationwide group of synthetic biologists from academia, industry, and government. Dr. Ellington recently gave a (virtual) talk to this group on "Applying molecular engineering to COVID-19." Dr. Ellington updated on the lab's efforts to develop POC (point-of-care) diagnostics, especially in response to potential reagent shortages. The LAMP-OSD assay developed by the Ellington lab can be readily adapted to cell phone detection or lateral flow assays (like pregnancy test kits), and can give an unambiguous yes / no answer within 30 minutes. New enzymes developed by the group have greatly improved the performance of this assay, and may prove useful for other COVID-19 diagnostics.
Detecting Life: Danny Diaz’s Doctoral Dissertation
Posted on September 10, 2020
Danny Diaz, a second-year graduate student under the instruction of Drs. Andy Ellington and Eric Anslyn, passed his PhD preliminary examinations and will now begin working on his doctoral dissertation. Danny's research focus lies at the interesting intersection of chemistry, biochemistry, and data science. Essentially, Danny is trying to make a tool that can detect life, by using machine learning and artificial intelligence to compare the materials properties of living systems (e.g. bark, skin, biofilms) with the materials properties of non-living systems (e.g. rocks, crystals, metals). Danny combines data collection using a variety of sophisticated methods such as NMR (nuclear magnetic resonance spectroscopy), LC/MS (liquid chromatography / mass spectrometry), and NGS (NextGen DNA sequencing) with novel machine-learning models that elucidate chemical complexity and how this complexity is partitioned between the biotic and abiotic chemicals and materials.
Using Graphene-Based Biosensors to Simultaneously Test for Influenza & SARS-CoV-2
Posted on August 13, 2020
As experts anticipate spikes in influenza and COVID-19 cases during the coming fall and winter seasons, researchers at the University of Texas at Austin are developing a biosensor that can distinguish between and test for the two illnesses simultaneously. Deji Akinwande, a professor in the Cockrell School of Engineering’s Department of Electrical and Computer Engineering, and his research team have recently received a grant from the National Science Foundation for their work on a graphene-based device that contains both anti-SARS-CoV-2 and anti-influenza antibodies. Different sections of the device are dedicated to antibodies for each virus, and the extreme sensitivity that graphene exhibits when a charged particle (such as a virus) is captured by the antibody may allow real-time, differential detection of viruses. While Dr. Akinwande has previously used graphene-based biosensors with anti-ferritin antibodies to detect iron deficiency in children, he stated “that just by changing the antibody, we [can] pivot the platform to focus on the coronavirus,” attesting to the adaptability of the biosensor. His team is currently working with Professor Andy Ellington’s lab to integrate the antibodies into the sensors, and hope to scale up device production in the coming months.
Simplifying the RT-qPCR Assay
Posted on July 6, 2020
Though the RT-qPCR assay is the gold standard for the detection of SARS-CoV-2, its complexity sometimes limits its use in either resource-poor settings or in circumstances where reagent availability has become limited. Searching for a simpler assay with similar detection performance, the Ellington Lab has previously advocated the use of a thermostable reverse transcriptase (RT) / DNA polymerase (DNAP), termed RTX. This enzyme has a relaxed substrate specificity, allowing it to perform as both a DNA- and RNA-directed DNA polymerase. However, the RTX enzyme is not yet as widely available as other industry standards that have been used for PCR for many years. In order to make a one-enzyme solution to RT-qPCR more widely available (which would greatly simplify reagent requirements), researchers in the Ellington lab wondered whether previously observed reverse transcriptase activity in the workhorse Taq polymerase might suffice. As described in this pre-print, the Ellington Lab found that optimized buffer and salt compositions allow Taq DNA polymerase to be used as the sole enzyme in TaqMan RT-qPCR reactions. These simpler assays perform comparably to the more complex original RT-qPCR assay, detecting as few as 2 copies / µL of input viral genomic RNA.
SynCell 2020: The Future of Synthetic Cell Technology
Posted on July 2, 2020
SynCell 2020, the International Conference on Engineering Synthetic Cells and Organelles, was virtually hosted by The University of New Mexico from May 26th through May 28th, 2020. The conference focused on the challenges and opportunities in synthetic cell technology, or in other words making cells from scratch! Topic areas included creating synthetic cells and organelles, spatial and temporal organization of these cytoplasmic structures, signaling and circuits, molecular machines, mechanics, motility, and the implications of synthetic cell technology. SynCell featured talks from world leaders in synthetic biology from premier American and German universities and labs, including our very own Dr. Andy Ellington from the University of Texas at Austin. At this virtual conference, Dr. Ellington organized and chaired a special panel on 'Future synthetic cell technologies for mitigation of viral pandemics,' that also included Dr. Kate Adamala (University of Minnesota), Dr. Eberhard Bodenschatz (Max Planck Institute for Dynamics and Self-Organization), and Dr. Michael Grunze (emeritus professor at the Institute of Applied Physical Chemistry at the University of Heidelberg). This distinguished international panel considered whether synthetic cells might be used in the future to produce or detect viruses, especially given the complexity of their glycosylation states and maturation processes, which are often difficult to engineer in the context of tissue culture cells or animal models. To the extent that synthetic cells might recapitulate key aspects of viral assembly or cellular pathogenesis, they could potentially prove to be extraordinarily useful vehicles for high-throughput drug screens, greatly accelerating the process of identifying lead compounds or therapeutic antibodies.
The Future of Cybernetics
Posted on May 27, 2020
In the past fifty years, we have witnessed the creation of cell phones, personal computers, GPS systems, and even the Internet. Inventions that once seemed outlandish have become necessary for keeping up with today’s fast-paced society. One can only wonder: if the last fifty years changed our world this drastically, what will come of the next fifty? Writing speculatively for the College of Natural Sciences at the University of Texas at Austin, Professor Andy Ellington discusses the future of cybernetics (the study of communications and automated control systems in machines and living things). His essay touches upon the shift from machines being regarded as extensions of humans to them fully replacing certain professions through advances in automation. Professor Ellington predicts that humans will need to adapt our own neural nets to catch up to machines and work with them. With the successes of present-day experiments demonstrating rapidly-advancing machine learning (virtual reality devices can now directly monitor our brain activity), we are not far from a future “where humans are something of a new ‘life’ form, more linked than ever to our computational devices.” Professor Ellington also emphasizes that steady advances in “neurobiology, electrochemistry, and synthetic biology” may soon take man-machine interfaces to the next level, allowing us to someday augment the physical bounds of our biological inheritance.
Fighting COVID-19: Providing Equitable Access to Biotechnology
Posted on May 26, 2020
As scientists from across the world battle the SARS-CoV-2 pandemic, global partnerships and networks have proven instrumental in allowing researchers to share resources and reagents. This is especially true since many resource-poor settings—and even settings with larger infrastructures under stress—must craft their own diagnostic solutions, especially when supply lines are stretched thin. Working with Dr. Jenny Molloy at the University of Cambridge, the Ellington Lab has contributed diagnostic reagents and methods to a network—Reclone.org—that is dedicated to providing equitable access to biotechnology for the current COVID-19 outbreak. As an example, the Ellington Lab has made available the enzyme known as RTX (Reverse Transcriptase Xenopolymerase), which performs both reverse transcription and PCR, yielding a single enzyme solution for RT-qPCR, the gold standard assay for the detection of SARS-CoV-2. In addition, new solutions for isothermal amplification reactions, which can be used for higher throughput screening of populations, are being put in place. In an era of social networking, it makes eminent sense that organizations such as Reclone.org can come online quickly and prove immediately useful, and the list of researchers and countries that are already involved speaks to the self-organizing networks of scientists who are expanding across the globe to quell the current pandemic.
Recognizing Our Dean’s Honored Graduates
Posted on May 14, 2020
As the school year comes to a close, we are pleased to announce that three undergraduate students in the Ellington Lab (Jose-Angel Torres, Matthew Duncan, and Vylan Nguyen) have been named 'Dean's Honored Graduates.' This is the highest honor awarded to UT Austin's graduating seniors and is restricted to fewer than one percent of the entire graduating class. During their time working with the Ellington Lab, each of these three individuals all made significant contributions to research, while also maintaining exemplary academic records.
Jose-Angel was a savant at instrument development, and 3D-printed a device for point-of-care diagnostics, and then assisted with the lab's development of a SARS-CoV-2 diagnostic that could potentially be run on the device. He is currently working on developing DIY methods for decontaminating personal protective equipment. Vylan also performed significant work related to the pandemic, developing cellular reagents that could lead to low-cost assays in resource-poor settings. She presented her research findings at the Undergraduate Research Forum last fall. Finally, Matthew has worked on projects at the intersection of synthetic biology and rational design. Applying his mathematical background to molecular biology, Matthew focused his research on designing novel genetic circuits to produce non-linear outputs.
Once again, we'd like to congratulate these three exceptional seniors on their amazing accomplishments! We wish them great luck with their future post-graduate endeavors.
Detecting SARS-CoV-2 With Isothermal Amplification Assays
Posted on April 30, 2020
As the COVID-19 pandemic continues, testing facilities (including hospitals and clinics) are searching for low-cost detection methods that use minimal resources and work quickly in point-of-care situations. This is especially true for resource-poor settings, or for screening and triaging potential patients prior to more exhaustive tests or treatment. To this end, researchers in the Ellington Lab have been designing and implementing isothermal amplification assays, which are reactions that—in contrast to the better known polymerase chain reaction—can multiply and detect target sequences, without the need for a complex infrastructure. Dr. Sanchita Bhadra recently published a preprint that shows how SARS-CoV-2 (the virus strain causing COVID-19) sequences can be detected via her proprietary “loop-mediated isothermal amplification” (LAMP) assays coupled with an oligonucleotide strand-displacement probe (LAMP-OSD). Remarkably, even though these assays can be carried out with essentially a heater (including something as simple as a hot glove) and detected with a cell phone, they have analytical sensitivities similar to those of gold-standard PCR assays. The assays even work in crude human saliva. Most importantly, they can be carried out with relatively crude enzyme reagents, which means that assays could be produced locally in resource-poor settings that might otherwise have difficulty finding or making assays.
Engineering Low-Cost, Scalable SARS-CoV-2 Tests
Posted on April 30, 2020
In the midst of a global COVID-19 pandemic, the Ellington Lab has been hard at work developing diagnostic methods to fill the testing gap. The lab’s utmost priority has been on developing and sharing reliable and scalable molecular diagnostics, especially for resource-poor settings. One assay type developed by the lab uses a novel reverse transcriptase previously created using directed evolution methods to make DNA copies of the SARS-CoV-2 RNA virus, which can in turn be amplified via the 'gold standard' RT-qPCR assay. The simpler 'one enzyme' assay the Ellington lab has developed has performed comparably to the more complex 'two enzyme' assays sanctioned by the CDC, and may be a boon for countries struggling with getting reagents. With a preprint detailing this assay, the Ellington Lab has made the development method readily available so researchers in low-cost and high-need settings can engineer their own assays. On the heels of this work, the Ellington Lab has developed isothermal amplification assays (so-called loop-mediated isothermal amplification using oligonucleotide strand displacement, or LAMP-OSD) as alternatives to the RT-qPCR method. Instead of requiring a devoted and somewhat complex machine for thermocycling, isothermal amplification assays can be carried out with equipment as simple as a hot glove and a cell phone. Again, this research has immense potential for areas lacking enough proper COVID-19 testing kits. The preprint on this method demonstrated successful detection of SARS-CoV-2 virions in crude human saliva. The Ellington Lab’s research has only been possible because of a strong network of collaborators, including the Sullivan Lab at UT Austin, the GSAF (Genomic Sequencing and Analysis Facility), and the Schoggins Lab at UT Southwestern Medical Center.
Undergraduate Vylan Nguyen Optimizes Cellular Reagent Development Methods
Posted on April 28, 2020
Underlying most molecular biology experiments and products are reagents, individual components of reactions. Often the most expensive (and more perishable) reagents are enzymes, catalysts that help perform reactions, such as amplification reactions for molecular diagnostics. However, this requires that enzymes be produced, purified, packaged ... all of which adds to their cost and complexity. This can make it very difficult for molecular biology, either research or medically-relevant, to be carried out in resource-poor settings. To solve this problem, the Ellington Lab has invented a new line of reagents, known as cellular reagents, which are cells that express the enzymes but are then freeze-dried (to kill the cells while preserving the enzymes within). Vylan Nguyen has been instrumental in helping to develop these reagents, and related that “when I started working on the reagents last year, I focused on making the original method—established by Dr. Sanchita Bhadra—easier to replicate, so that the reagents could be made locally at the labs they were to be used at.” Vylan altered this method in three ways to drop the cost and make it more replicable. Initially, she optimized how users can add reagents to the reaction mix, using lyophilization (freeze drying) to bind the cells to small 3mm glass-fiber disks. Instead of having to hydrate the reagents and pipette them into the reaction, one can simply drop these disks into the reaction tube! Next, Vylan optimized the visual output of cellular reagent reactions (so users can easily see reaction results) by changing the concentration of reagents per cell. Lastly, she further modified the lyophilization step to reduce cost, keeping the dehydration idea but changing the overall process to desiccation, an alternate method that uses air-drying instead of a costly lyophilization machine. In consequence, the cellular reagents now cost approximately 85% less and can be shipped/stored at room temperature for more than three months. Although Vylan originally was developing kits for water quality analysis, her work has become instrumental in the distribution of low-cost assays for COVID-19. Vylan’s work would not be possible without many collaborative contributions, including from Jose-Angel Torres, another undergraduate in the Ellington Lab, who designed a low-cost 3D-printed visualization box for these assays, and researchers in various facilities throughout Africa who have field-tested the cellular reagents.
Here’s a diagram that shows the cellular reagent development process!
Undergraduate Jose-Angel Torres Creates PPE Decontamination Device from Home
Posted on April 23, 2020
Jose-Angel Torres, an undergraduate student with the Ellington Lab, has ingeniously repurposed a commercially-available ozone generator into a low-cost (~$100) PPE (personal protective equipment) decontamination device from inside his own home! Seeing his parents risking their health every day as essential workers during the ongoing COVID-19 pandemic, Jose was motivated to keep them out of harm’s way and “give them peace of mind that their equipment would be safe” for repeated uses. Jose was inspired by ozone’s use as a cleaning agent in the real-estate and water-treatment industries and deduced that ozone decontamination, a low-temperature process, would be ideal for cleaning PPEs (many of which are made of unwoven thermoplastic fibers and are resistant to thermal stress). Jose’s device (pictured) consists of an ozone generator inside of an airtight polypropylene container, which allows ozone to accumulate and circulate—the generator’s internal fan not only cools the machine, but also pushes ozone around inside the container. In just over an hour, any PPE placed inside Jose’s device is decontaminated. Jose admits that his device, as useful as it is, needs future iterations to increase its efficiency, but for now, it’s doing fine and is also used by his family to decontaminate shoes, clothing, and packages.
Ellington Presents at the Sixth Annual IEEE EMB Strategic Conference
Posted on December 15, 2019
The sixth annual IEEE EMB (Engineering in Medicine and Biology) strategic conference was held in Maryland from November 20th through November 22nd of this year. The conference focused on Health Innovations, specifically POCT (Point Of Care Technologies), and provided a “strategic forum in which clinicians, industry experts, innovation experts, researchers and students will examine how to define unmet clinical needs and successfully travel along the innovation cycle towards commercialization and patient impact.” The main goal of this conference was for stakeholders to explore these technologies and collaborate to improve healthcare at an affordable cost. Dr. Ellington from the University of Texas was in attendance and gave a talk on “Synthetic Biology/Gene Editing’s Role in Diagnostics”. Dr. Ellington provided insights into the difficult task of reducing complex technologies to the bedside and beyond, where simplicity is more important than scientific novelty. In particular, he discussed how simple isothermal amplification and simple oligonucleotides probes (so-called LAMP-OSD) may be vastly superior to CRISPR-based methods for diagnostics.
AI Protein Solutions Travels Across the US as a part of the ICORPS Program
Posted on November 3, 2019:
Earlier this year, Austin Cole, Raghav Schroff, Danny Diaz, and Dr. Ross Thyer developed a machine learning algorithm to predict the identity of functional amino acids in protein sequences with high accuracy (Speeding up Evolution using AI). They have now translated this technology into a company, AI Protein Solutions. Recently, the company and corresponding team of inventors was selected to be a part of the ICORPs Program of the National Science Foundation (NSF), which prepares scientists and engineers to get their products from the laboratory to the market. “The technologies that we as engineers come up with and the products we design are far short of a company,” explained Austin Cole. “The ICORPS Program introduced us to factors involved in taking our product and turning it into a commercial endeavor, such as finding competitors, reaching customers, and other business networking skills.” In 7 weeks time, the team flew around the country on 9 trips and ultimately interviewed 66 companies relevant to their product. These trips provided insights into many of the problems that AI Protein Solutions hopes to solve, and the team believes it can use the advanced neural network they have generated to improve the structure and function of enzyme catalysts for textile, agricultural, bioprocessing, and therapeutics applications. While the exact individuals and companies the team spoke with remain confidential, they found productive and active partnerships, and are in the process of starting work with them. “We came out of the program with a better understanding of how to bridge the gap between the business side and the technical side,” The experience gained through the ICORPs Program was invaluable, and according to Cole while “there is no business training for technical individuals, and while being tech savvy is important, learning about business mechanics is essential when making a company. While the quality of your product is obviously important, the trust that the company confides in you and the relationships that you build are most essential, since they will be trusting you to solve their problems.”
Project DREAM: Using Aptamers to Decrease Side-Effects of Anti-Cancer Drugs
Posted on October 28, 2019:
Project DREAM, led by Principal Investigators Dr. Carla Cruz (University of Beira Interior) and Dr. Andy Ellington (University of Texas at Austin) aims to mitigate the harmful side effects of anticancer drugs by using a unique nanosystem to target tumor cells and prevent healthy tissues from exposure to the otherwise toxic drugs. Recently, Dr. Cruz and Dr. Ellington were interviewed by a representative from the UT Austin Portugal Program (a major partnership program in between the Portuguese Foundation for Science and Technology and UT) regarding their unique approach and explained how an aptamer known as AS1411 could be modified to better carry drugs to tumors. “Previously, it was demonstrated that these aptamers can selectively deliver anticancer ligands,” Dr. Cruz said, such as acridine orange derivatives, and showed improved selectivity towards cancer cell lines. However, she continued, “moderate concentrations and long incubations were required to observe cytotoxicity.” In order to improve the selectivity and efficacy of the aptamers, they were conjugated to gold nanoparticles, which are preferentially internalized by tumor cells. Better cytotoxic effects were achieved with shorter incubation periods (2 days). The DREAM project ultimately includes researchers from two Portuguese laboratories (CICS-UBI and C2TN-IST), a public hospital (CHCB), a company (Labfit-HPRD) and the Ellington Lab from UT Austin, and overall the team hopes to move compounds towards clinical utility within 5 years via the COST Action program (a network for nationally funded research projects).
U.S. Army Research Initiative Meeting held in Austin to discuss Creation of new types of Polymers
Posted on October 16, 2019:
On October 10, the Army Research Office (ARO) MURI award headed by Michael Jewett at Northwestern University was held in Austin, Texas, with collaborators Eric Anslyn (Chemistry), Andy Ellington (Molecular Biosciences), Charles Schroeder (University of Illinois Urbana Champaign(UIUC)), Jeff Moore (UIUC), Eric Gaucher (University of Georgia), and Rhiju Das (Stanford University). This diverse team is attempting to recast the ribosome not as a protein-making machine, but as a more generic polymer-making machine. Already, recombinant protein production by the ribosome has transformed the lives of millions of people through the synthesis of biopharmaceuticals, like insulin, and industrial enzymes, like subtilisin, that are used in laundry detergents. In nature, however, only limited sets of protein monomers are utilized, thereby resulting in limited sets of biopolymers (i.e., proteins). Here, the team seeks to expand nature’s repertoire of ribosomal monomers to yield new classes of enzymes, therapeutics, materials, and chemicals with diverse genetically encoded chemistry. To this end, they have developed new technologies for charging tRNAs with non-amino acid substrates using Flexizymes (ribozyme tRNA synthetases) and have engineered other aspects of the translation machinery, including Elongation Factor Tu and the ribosome itself, to be able to utilize these non-standard monomers to make decidedly non-protein polymers. Overall, the goal of the group is to develop a means of making sequence-defined, electronically active polymers for any of a variety of applications of commercial and defense importance.
Cannabis: The Future of Pain Alleviation?
Posted on September 23, 2019
Dr. Andy Ellington and his team from the Center for Systems and Synthetic Biology have been awarded a grant from the National Center for Complementary and Integrative Health (NCCIH) to search for and better understand minor compounds produced by cannabis that could potentially aid in the alleviation of pain (https://nccih.nih.gov/news/press/09192019). To this end, Dr. Ellington and his co-workers have developed an extremely novel system for the production and assay of cannabinoids ... in yeast! By using yeast as vehicles for screening, rather than plants, it becomes far easier to divide down the heady chemical mixtures that are present in the plant, and better define the particular active agents and what pain receptors these active agents may act on. The use of cannabinoids like CBD as a treatment for chronic pain has become increasingly popular, and might one day even serve as an alternative to opioids, which are highly addictive and aren’t as effective in the long run.
Cellular reagents make their mark in Africa
Posted on September 23, 2019
Earlier this year, Dr. Sanchita Bhadra and her team from the Ellington Lab at UT Austin built a kit that would make research easier to conduct in low resource areas. The kit is intended for students and instructors in these low-resource areas due to its cost effectiveness and ease of use. This would especially prove beneficial in giving research opportunities to aspiring researchers in need of a lab, allowing them to carry out procedures such as PCR using cellular reagents. (https://ellingtonlab.org/archive/2019/7/8/a-solution-to-research-in-low-resource-areas)
Since then, Dr. Bhadra and her team have also been working with scientists at Cambridge University and their research partners in various African countries to assess the utility of cellular reagents in molecular biology research and education. In initial studies, ready-to-use cellular reagents were sent to researchers in Cameroon and Ghana who were able to successfully perform PCR using these reagents. Cellular reagents seamlessly replaced pure enzymes in existing PCR protocols and performed robustly despite the vagaries of shipping and variations in humidity and temperature during storage. These exciting results demonstrating cellular reagents to be reliable alternatives to expensive pure enzymes have paved the way towards efforts in local production and more extensive outreach. Researchers in both UK and Africa are beginning to use expression constructs and production protocols developed in the Ellington Lab to undertake in-house production of cellular reagents. Starting with these foundational efforts, our global team aims to develop, test, and make freely available a comprehensive suite of common enzymatic reagents for molecular and synthetic biology.
SynCell 2020: Engineering Synthetic Cells and Organelles
Posted on September 10, 2019
SynCell 2020, the International Conference on Engineering Synthetic Cells and Organelles, will be held from May 11th through May 14th, 2020 in Santa Fe, New Mexico (https://syncell2020.unm.edu). The conference will focus on the challenges and opportunities in synthetic cell technology, or in other words making cells from scratch! Topic areas for the main program will include creating synthetic cells and organelles, spatial and temporal organization of these cytoplasmic structures, signaling and circuits, molecular machines, mechanics, motility, and the implications of synthetic cell technology. SynCell will feature talks from world leaders in synthetic biology from premier American and German universities and labs, including our very own Dr. Andy Ellington from the University of Texas at Austin, who will be discussing how DNA nanotechnology and protein engineering can impact the de novo development of cells. Talks will range from the engineering of biomolecular systems (Matthew Lakin, University of New Mexico) to the potential applications and simulations of these systems (Kate Adamala, University of Minnesota). An evening poster session and other dedicated times for free-form discussion are also planned. A featured translational speaker, Mike Jewett, will explore issues related to working with industry on the commercialization of synthetic cell technologies, and an industrial forum is planned for after Dr. Jewett’s talk. Finally, the first day of the conference consists of an interactive educational component for students and aspiring researchers.
DNA25 Meeting held in Seattle, Washington
Posted on August 27, 2019
The international DNA nanotechnology meeting, DNA25, was held this year in Seatlle, Washington on the University of Washington campus. This is the annual gathering of researchers interested in all aspects of DNA computation, and this year there was a focus on the use of DNA as a potential alternative to silicon as an information storage medium. Surprisingly, it may soon be cheaper to store archival data as nucleotides (GATC) rather than as digital flips in a memory core. Key issues that remain to be solved include how to access and easily read out the data, a problem that was considered in depth by another University of Texas at Austin researcher, David Soloveichik of the Electrical and Computer Engineering Department. In addition to delivering a talk on manipulation xenonucleic acids (XNAs) for computational applications, Dr. Ellington participated in a panel on the future of the field (see picture). This panel included Dr. Ned Seeman, widely regarded as the founder of DNA nanotechnology; Shelley Wickham of the University of Sydney; Anne Condon, from the University of British Columbia; and William Shih of the Wyss Institute at Harvard.
Ellington Lab Represented at EBRC Symposium in Washington D.C.
Posted on August 20, 2019
On August 1 & 2, the Engineering Biology Research Consortium (EBRC) held a symposium in Washington D.C. titled ‘The Convergence of Engineering Biology & Data Science: Understanding Risk and Mitigation Options’. The discussion was focussed on how computer and data science is impacting security in the field of biological engineering, and strategies to mitigate these issues. Talks were wide-ranging, from field overviews (Richard Murray, Caltech) to technical contributions (Lance Stewart, Center for Protein Design UW). Graduate student Austin Cole represented the Ellington Lab and a new start-up company, AI Protein Solutions, and presented a talk titled “Structure Based Machine Learning for Protein Engineering.” The talk was an outgrowth of novel neural network analyses of protein structure and stability, but was canted towards the possibilities inherent in using AI to predict and counter emergent biothreats. Speakers were drawn from top biological engineering laboratories in both academia and industry. The audience was composed entirely of Government stakeholders from a variety of agencies. Attendees discussed strategies that might be used to preemptively identify biological threats as well as how better risk assessments might be carried out.
Ellington Delivers Lecture in New York for a Synthetic Biology Course
Posted on August 9, 2019
On July 30, Dr. Ellington visited Cold Spring Harbor Labs (CSHL) in New York to deliver a lecture to the Synthetic Biology Summer Course, "The Tenuous Balance Between Systems and Synthetic Biology." Because of the centrality of both systems and synthetic biology in the Center for Systems and Synthetic biology (duh), Dr. Ellington could bridge between Ed Marcotte's fundamental work on phenologs and yeast humanization to his own work on augmenting the genetic code and developing orthogonal control systems for organisms. The CSHL course is a mainstay of students learning to enter the field of synthetic biology, and the diversity in backgrounds was fascinating. The beer was even better (still not sure about the raspberry ale).
AbSciCon 2019: Detecting Agnostic Biosignatures on Other Planets
Posted July 28, 2019
At the end of 2018, Dr. Andy Ellington and Dr. Eric Anslyn from the University of Texas at Austin, among 13 other scientists, were awarded a grant from NASA totaling nearly $7 million to continue research in detecting extraterrestrial life. This comes as a part of NASA’s Astrobiology Program, which is working to find life on neighboring planets using what’s called LAB, the Laboratory for Agnostic Biosignatures. In June 2019, Dr. Ellington and Dr. Anslyn attended AbSciCon, NASA’s Astrobiology Conference, and discussed efforts to detect these “agnostic biosignatures of life”.
“The signals we are looking for are chemicals that are so complex that they could only have been created by some form of life,” says Dr. Anslyn. Really, any type of signature could be possible, although proteins and nucleic acids like that of humans are unlikely. “Since we don’t know what type of signal to expect, we need an agnostic method to detect life,” he further explains.
NASA also announced its “Dragonfly Mission” and presented the mission’s commander at AbSciCon 2019. Dragonfly’s goal is to create a probe that will launch in 15 years to Titan, one of Saturn’s moons, will take 8 additional years to reach its destination, and look for hints of life. While NASA is working to engineer this complex machinery, Dr. Ellington, Dr. Anslyn, and others are working together to develop chemical tests that NASA’s machinery would implement. In the near future, we hope to discover more about our neighboring planets, and what inhabits them.
A Partnership with the Texas Department of Health to Detect Wolbachia in Harris County Mosquitoes
Posted July 26, 2019
Mosquitoes are known for housing a variety of nasty diseases, from Zika to dengue to yellow fever. As the weather begins to warm up, we want to enjoy the warm Texas sun. Unfortunately, so do the mosquitoes. Since these blood sucking creatures carry a variety of diseases, they make it difficult to enjoy the summertime. Mosquitoes that are infected with the bacteria Wolbachia however, have a reduced ability to transmit viruses to people, such as Zika or dengue. Dr. Sanchita Bhadra of the Ellington Lab in collaboration with Dr. Tim Riedel and his students in the DIY Diagnostics Freshman Research Initiative stream have developed an easy way to test mosquitoes to find out if they carry Wolbachia within tens of minutes, using LAMP-OSD.
Earlier this year, Drs. Dagne Duguma and Mustapha Debboun from the Harris County Mosquito and Vector Control Division of the Texas Department of Health visited UT Austin to observe a demo of the Wolbachia test. They talked in detail with Dr. Bhadra and DIY Diagnostics undergraduate researcher, Simren Lakhotia, regarding application of this LAMP-OSD technology to facilitate vector surveillance in Harris County. “The representatives from Harris County were visiting us because they are interested in using our LAMP-OSD assay to test for Wolbachia in mosquitoes,” explains Dr. Bhadra. “We are getting ready to send them 100 Wolbachia tests, with which they will test mosquitoes collected from various regions in Harris County” she further stated. If successful, this pilot test will set the groundwork for developing and applying a larger suite of molecular testing methods for vector surveillance. By learning more about the environment around us, we can begin to address the public health problems plaguing us.
Drs. Ellington and Anslyn Present Efforts to Improve Science Education at Annual HHMI Meeting
Posted July 25, 2019
Dr. Eric Anslyn and Dr. Andy Ellington were present at the annual meeting on the Howard Hughes Medical Institute (HHMI) compound in Chevy Chase, Maryland. The meeting was hosted by the HHMI Professors Program, a program empowering research scientists to extend engaging research opportunities to undergraduate students and improve science education. They presented both a lightning talk (Dr. Ellington) and chalk talk (Dr. Anslyn) on their conjoined efforts to develop professional and entrepreneurial education for undergraduates. Specifically, they presented their program known as Translational Research Initiative Professional (TRIP), which gives undergraduate chemistry majors first-hand experience of what it is like to be a graduate student in chemistry, as well as a close look at the lifestyle and career of chemistry professors.
In addition to presenting their own efforts, they also interacted with a wide array of other Hughes’ Professors, who were promoting projects ranging from increasing the representation of underrepresented minorities in astronomy (Keivan Stassun, Vanderbilt) to carrying geoscience back to students’ home communities (Julia Clarke, University of Texas at Austin) to veterans’ involvement in the sciences (Dr. Marla Geha, Yale). Since the program began in 2002, sixty-nine scientists have been named HHMI professors, working to support students in their path to STEM related careers.
Early Exposure to Scientific Research: A New TIDES/FRI Program
Posted July 23, 2019
In order to train the scientists of the future, they should be exposed to cutting edge approaches now. This of course is what a modern research University does; it provides undergraduates with access to key thought leaders and research resources that enable STEM career paths to be built and taken. But why wait until college to start this process? The TIDES program and the Freshman Research Initiative at the University of Texas offers research opportunities to high school students, placing them in labs for a summer experience through the High School Research Academy. This program has been placing students in the Ellington Aptamer FRI research stream for the past eight years, allowing the students to decide what projects and procedures to carry out. Additionally, the students have seen successes in iGEM science competitions, winning gold in 2015, as well as bronze in 2017 and 2018. Now, the Ellington lab has developed a program to bring high school students into research labs for longer internships that last through the entire academic year. As a result, in addition to early training and prolonged exposure to the sciences, the high school students will gain critical presentation skills from exhibiting their work in international competitions such as iGEM and Intel ISEF. By granting them additional time in the lab, these students are able to not only develop thorough research ability, but interact with local and global experts alike, allowing them to develop a network which they can leverage throughout their careers.
Ellington Receives Research Foundation’s STAR Award
Posted July 15, 2019
On July 12, 2019, Dr. Ellington received the Research Corporation for Science Advancement's (RCSA) STAR award for his work on entrepreneurial education. In partnership with Dr. Sarah Eichhorn and the Texas Institute for Discovery Education, Dr. Ellington has helped to establish the Inventors' Program, where students can take on translational problems and learn business-ready skills. As an example, Simren Lakhotia, an undergraduate researcher in the program, has worked on the development of a portable field diagnostic for Rocky Mountain spotted fever that would allow hikers to test individual ticks for the disease. Dr. Ellington was originally a Cottrell Scholar, an award that allowed teaching and research to be melded, and has since maintained a long association with the Research Foundation, an organization devoted to advancing science education.
A Possible Bridge Between the Modern Protein-Based world and a hypothetical “RNA World”
Posted July 11, 2019
On July 11, 2019, Dr. Ellington delivered a short talk and poster at the 19th Human Frontiers Science Program (HFSP) Conference, detailing progress by an international team on "Rebuilding and reimagining the last common ancestor, a ribo-organism." In this bold project, Dr. Ellington is collaborating with Dr. Hiro Suga (University of Tokyo), Dr. Michael Jewett (Northwestern University), and Dr. Philippe Marliere (Université Evry) on replacing the machinery responsible for enforcing the genetic code, protein tRNA synthetases, with ribozymes that can perform similar tasks. In doing so, the team hopes to return living systems to an earlier state — a transitional organism that bridged between a hypothetical "RNA world" where ribozymes ruled and the modern protein-based world. In addition, given the facility with which ribozymes can be reprogrammed, the engineering of such an organism would offer many opportunities for changing and expanding the genetic code, leading to many possible biotechnology applications.
Two UT Scientists Helping to Detect ‘Life As We Don’t Know It’
Posted June 26, 2019 from an article in UT News
Two University of Texas at Austin faculty members have joined an interdisciplinary scientific team that is working with NASA to research new approaches to detecting extraterrestrial life. The UT Austin team will receive more than $722,000 over five years for the NASA project, which aims to develop methods to detect life on other worlds that might look nothing like life on Earth.
February 22, 2019: DNA Gets a New — and Bigger — Genetic Alphabet. New York Times
DNA is spelled out with four letters, or bases. Researchers have now built a system with eight. It may hold clues to the potential for life elsewhere in the universe and could also expand our capacity to store digital data on Earth. (Read the full news article or read the paper!)
February 22, 2019: Anna’s project is front page of Nature Chemistry.
The biological function of many proteins requires their assembly into a specific multi-protein structure. Designing artificial protein assemblies is difficult, however, and often relies on the precise redesign of protein–protein interfaces. Now, David W. Taylor, Andrew D. Ellington and colleagues have shown that supercharging green fluorescent protein enables variants of alternating net charge to assemble into a variety of well-defined architectures. The front cover shows a symmetrical 16-mer structure composed of two stacked rings of octamers.
January 18, 2019: A project which the Ellington laboratory is working on is on the news. The UT Austin chemistry team has received a $722,000 NASA grant to establish new methods that show the proof of life outside the Earth.
August 30, 2018: Simple test detects disease-carrying mosquitoes, presence of biopesticide. Sanchitas’ research on Zika is on Science Daily
September 7, 2016: Andre's latest paper on evolving orthogonal suppressor tRNAs for modified amino acid incorporation is now available to read.
July 18 - 21, 2016: Several members of the lab attended SEED 2016 in Chicago, where Andy spoke about the functional incorporation of unnatural amino acids into proteomes.
June 24, 2016: Research by Jared, Jimmy, and Raghav on the development of a reverse transcriptase capable of proofreading is featured in this week's issue of Science.
Summer 2016: Eric Verbeke joins the lab as a summer rotation student. Welcome Eric!
May 25, 2016: Bo's paper on anti-ricin antibody discovery through repertoire analysis and yeast surface display is out.
May 23, 2016: The new lab website is under construction.
April 29, 2016: Jared successfully defends his dissertation.
March 31, 2016: A new paper by Cheulhee on expanding oligonucleotide terminal hairpin formation and self-priming (THSP) by incorporating phosphorothioates is now available.
March 23, 2016: Sherry successfully defends her dissertation.