2021-2022 GUIDEBOOK CONTENTS
About HudsonAlpha Institute for Biotechnology . ...............................2–3 HudsonAlpha Blogs & Podcasts ...............................................................4 Life Science Educator Resources .............................................................5 Executive Summary ..................................................................................6 Science Snapshots ....................................................................................7 New Findings . .....................................................................................8–17
Recent research findings provide a quick update on the genetics, genomics, and biotechnology field. This section represents discoveries, treatments or applications that have been announced during the past year.
Infographic on Genomics-Driven Oncology .....................................18–19 HudsonAlpha Digital Applications .........................................................20 Snapshot References & Image Credits ..................................................21
ONLINE BIOTECH BASICS
Looking for a place to start? HudsonAlpha offers easy-to-understand explanations of foundational concepts at hudsonalpha.org/biotech-basics. Twenty-four key technologies or concepts are described in detail.
Language and concepts are intentionally geared to a high school or public audience.
science for life ®
About HudsonAlpha The HudsonAlpha Institute for Biotechnology is a nonprofit institute dedicated to developing and applying scientific advances to health, agriculture, learning and commercialization. Opened in 2008, HudsonAlpha’s vision is to leverage the synergy between discovery, education, medicine and economic development in genomic sciences to improve the human condition around the globe. The HudsonAlpha biotechnology campus consists of 152 acres nestled within Cummings Research Park, the nation’s second largest research park. The state-of-the-art facilities co-locate nonprofit scientific researchers with entrepreneurs and educators. HudsonAlpha has become a national and international leader in genetics and genomics research and biotech education. It includes more than 45 diverse biotech companies on campus.
HudsonAlpha scientists are adding to the world’s body of knowledge about the basis of life, health, disease and biodiversity and seeking to enable:
Genomic Research
● Earlier and/or less invasive diagnostics ● Better, more customized treatments for disease ● Improved food, fiber and energy sources
Significant Research Publications Our research- ers have been published in more than 900 scientific publications since the beginning of HudsonAlpha in 2008 to help secure a global leadership position in genomic research.
Current research focus areas are:
Foundational Research
Plant Science and Sustainable Agriculture Applying genomic knowledge to agriculture and bioenergy to create a more sustainable world
Genomic Health Leveraging the power of the human genome to diagnose, predict and prevent disease as well as helping others incorporate genomics into practice
Research that improves the under- standing of biological phenomena. Includes studies of natural variation, principles of bioethics, and computa- tional biology and bioinformatics
Human Health
Neurological and Psychiatric Disorders Including Alzheimer disease, Parkinson disease, ALS, Huntington disease, bipolar disorder, schizophrenia, autism and epilepsy
Rare disease Undiagnosed childhood genetic disorders
Cancer Multiple forms of cancer, including breast, ovarian, prostate, kidney, brain, colon and pancreatic
Immunogenomics Application of genomic technology to understand the immune system’s role in health and disease
Autoimmune diseases Including lupus, rheumatoid arthritis, and other complex autoimmune diseases.
Global Footprint of Research Partnerships
HudsonAlpha partners with other research institutes and life sciences companies around the globe – and even in space – to make genomic discoveries.
Government support comes from: National Science Foundation U.S. Department of Energy Joint Genome Institute U.S. Department of Agriculture National Institutes of Health
National Human Genome Research Institute National Institute of Arthritis, Musculoskeletal and Skin Diseases National Heart, Lung and Brain Institute National Institute of Mental Health National Institute of Environmental Health Sciences
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Educational Outreach
HudsonAlpha’s Educational Programs HudsonAlpha's Educational Outreach team inspires and trains the next generation of life science researchers and workforce while building a more genomically-literate society. The dynamic educators at HudsonAlpha reach students, educators, medical practi- tioners, and the community through hands-on classroommodules, in-depth school and workshop experiences along with digital learning opportunities. HudsonAlpha also provides educational opportunities for healthcare providers and learning tools for patients who are making medical decisions using their personal genomic information. Additionally, the team builds genomics awareness through community outreach classes and events. Annually, these combined programs and resources reach more than 1 million individuals.
Educator Professional Learning HudsonAlpha has several opportunities for teacher professional learning, ranging from single-day workshops to ongoing classroom support. These increase an educator’s comfort in discussing genetic concepts and terminology along with the associated ethical, social and legal issues.
Student Experiences Field trips, classroom visits by industry leaders, summer camp sessions, in-depth internship opportunities and college-level laboratory courses engage students in biotechnology-related fields, increase exposure to career options, provide mentoring opportunities and equip students with a toolbox of content-specific skills.
Classroom Kits and Digital Resources HudsonAlpha has developed kits and activities to engage elementary and middle school students in hands-on experiences that match state curriculum requirements related to DNA and genetics. Multiple laboratory activities have also been crafted for students in grades 9-12. Activities highlight topics such as trait inheritance patterns, extracting DNA, exploring chromosome behavior in cells, diagnosing genetic disorders, and using bioin- formatics databases. Many of these resources are commercially available to classrooms around the nation through a partnership with Carolina Biological (www.Carolina.com).
Clinical Applications HudsonAlpha is empowering patients to be informed genomic healthcare consumers and members of society. Our genetic counselors are involved in providing patient education and support for clinical and research activities across the Institute. The genetic counseling team also provides education and training programs for healthcare providers and trainees to support the integration of genomics into routine and specialized medicine.
Biotech Enterprises
HudsonAlpha strengthens and diversifies Alabama’s economy by fostering success in life sciences companies of all stages and sizes. Its 152-acre biotech campus within Cummings Research Park supports more than 45 tenant companies, from startups to global leaders, with space for more. HudsonAlpha offers turnkey and build-to-suit laboratory and office space for lease in an energizing environment with superior shared amenities. Bioscience enterprises on campus benefit from access to HudsonAlpha researchers as well as strategic support through investor forums, workforce and business assistance, marketing resources and bioscience networking events.
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SCIENCE FOR LIFE
Blogs & Podcasts
Dr. Lamb’s blo
In a field that pushes the boundaries of human discovery daily, keeping the conversation current matters a great deal. In Shareable Science blog, Dr. Lamb breaks down topics that show up everywhere from television news shows to watercoolers of research institutes around the world.
www.shareable-science.org
Welcome to Everyday DNA, the blog that takes you inside the science behind HudsonAlpha’s discoveries. Together, we will explore topics like DNA sequencing, sustainable agriculture, genetic diseases and disorders, and much more. Basically, if HudsonAlpha scientists study it, we will cover it. We hope that each post will bring you one step closer to understanding and appreciating the science that is a part of our everyday world.
Sarah Sharman PhD HudsonAlpha Science Writer
www.hudsonalpha.org/everyday-dna
TINY EXPEDITIONS PODCAST Welcome to season 2 of Tiny Expeditions , a podcast that explores the tiny science of genetics, DNA and inheritance. In this season we will be looking at what tiny science can tell us about the world of agriculture. We’ll talk about how genetics may have saved your favorite candy bar, what happens when you put plants in space, can a weed save the world or science help create the perfect craft beer? Listen to season 1 on your favorite podcast app or at www.hudsonalpha.org/tinyexpeditions/ . Season 2 coming October 2021.
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Life Science Educator Resources
For High School Educators
Genetic Technologies for All Classrooms (GTAC) is an intensive professional learning experience offered at HudsonAlpha Institute for Biotechnology that prepares science educators to address high school-level genetics, genomics and biotech content. To learn more about the various GTAC offerings, visit www.hudsonalpha.org/gtac .
GTAC
This round of GREAT , our fifth round- GREAT V, focuses on current and emerging applications of genetic technologies poised to impact our daily lives. From new uses of DNA technology in criminal investigation, to under- standing the nuances of familial inheritance patterns, this round has something for everyone! Join us for a rich learning experience packed with new content, and take home two new pilot kits to field test in your classroom. Learn more at www.hudsonalpha.org/great .
For Middle School Educators
LifeScience Links is a summer professional learning experience that provides seventh-grade life science teachers updated content knowledge, engaging strategies and authentic lab experiences. Educators leave the workshop equipped to link Course of Study Standards to real-world biotech applications and careers. Learn more at www.hudsonalpha.org/lifesciencelinks .
Educator Resource Hub
The HudsonAlpha Educator Resource Hub is your one-stop shop for support- ing materials, some developed by HudsonAlpha and some created by partner educators. Scroll through the categories to find free lesson plans, activities, digital tools and classroom content tips. Resources are curated by content, type of resource and developer. Designed to enhance your life science instruction at multiple grade levels, these resources are freely available and updated often.
www.hudsonalpha.org/educatorhub/
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SCIENCE FOR LIFE
EXECUTIVE SUMMARY
Throughout the COVID-19 pandemic, the scientific process has claimed center stage. On the one hand, it’s been inspiring to witness scientific and clinical experts focused on this single issue with laserlike intensity. Global findings have been gathered, ana- lyzed, and rapidly shared. Phrases like PCR, rapid antigen tests, neutralizing antibod- ies, and viral genome sequencing, have become part of the public consciousness. On the other hand, the process has been messy and convoluted. Scientists some- times use different vocabulary, leading to public misunderstanding and confusion. Often, there are no universal guidelines to collect and evaluate data making it hard to compare findings from different groups. Consequently, scientists argue over meaning and next steps leading at times to conflicting and changing recommendations. Scientific discovery doesn’t follow a straight path. Early findings can often leave room for many explanations with clarity finally emerging through rigorous review of the data and follow-up research. However, these things take time. This is true for understanding pandemics, but also for hundreds of complex topics like determining disease risks, identifying sustainable energy sources, and modeling climate change. Noted biochemist and American author Isaac Aismov once said “Science is uncertain. Theories are subject to revision; observations are open to a variety of interpretations, and scientists quarrel amongst themselves. This is disillusioning for those untrained in the scientific method” . We see this disillusionment firsthand. The absence of straightforward answers opens the door to conspiracy theories and misinformation. We choose sound bites and overly simplistic solutions over the complicated nuances of the real world. The scientific community must do a better job of explaining the data and cultivating scientific literacy. Our world is increasingly shaped by scientific discovery and tech- nological innovation. If people don’t grasp the concepts and implications, informed decision-making about how it should be used will grind to a halt. It’s for that reason HudsonAlpha generates the annual Biotechnology guidebook. This year’s edition features 48 new research findings related to genomics and biotechnology, described in jargon-free language. They cover a range of scientific applications from human health to sustainable agriculture. Yes, you’ll find information about COVID-19 as well. Each story links to the original research article, preprint or data source. Foundational explanations about the science behind the research can be found in our Biotech Basics series at hudsonalpha.org/biotech-basics.
Neil Lamb PhD
I’ve enjoyed gathering and compiling these discoveries. I hope you enjoy reading about them.
A huge shout-out to the HudsonAlpha writers, designers, reviewers and advisors who made this edition of the guidebook both readable and visually compelling. Thank you Sarah Sharman, Cathleen Shaw, Madelene Loftin, Stacey Brewer, Jennifer Hutchison, Dasi Price and April Reis. —I’m beyond grateful for your time, talent and support.
Neil E. Lamb PhD Vice President for Educational Outreach HudsonAlpha Institute for Biotechnology email: nlamb @ hudsonalpha.org twitter: @ neillamb
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SCIENCE SNAPSHOTS a quick summary of 10 genetics and biotech stories 1. Researchers recently published a catalog of DNA variation in the soybean genome. More than 15 million genetic changes were identified across 1,000 different soybean plants gathered
6. In 2003, the Human Genome Project (HGP) sequenced the first near complete human genome, resolving all but about 15 percent of the genome that mostly contained repetitive regions that were inaccessible using the technology at the time. Extensive work since the completion of the HGP brought the missing parts down to about eight percent. Now an in- ternational team of scientists from the Telomere-to- Telomere Consortium claims in a pre-print to have sequenced a complete, gapless human genome. Using a relatively new type of sequencing technology called long-read sequencing, more than 3,000 predicted genes were identified, including about 150 new protein-coding genes. More details can be found in the Shareable Science blogpost: How does genomics and genetics impact our world today? 7. During summer 2021, the UK-based biotech company Oxitec conducted first US field test of genetically modified mosquitoes. Nearly 144,000 modified male mosquitoes were released across regions of the Florida Keys. When the mosquitoes mate with females, they pass on a gene that prevents female offspring from reaching maturity. If this approach successfully reduces the number of females, it could one day be used instead of pesticides. Controlled field releases in other countries have led to a drop in mosqui- to-carried diseases. Oxitec has been working with various Florida communities for over a decade to design this pilot and educate stakeholders.
The laboratory of HudsonAlpha faculty researchers Jane Grimwood PhD and Jeremy Schmutz contributed to this work. from around the world. These include mutations that silence over 10,000 soybean genes. This catalog of DNA change can be used to identify the genetic basis of important soybean traits and guide efforts to breed more sustainable plants.
2. The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for their work developing amethod for genome editing using the CRISPR/ Cas9 system. The pair began collaborating in 2011 and early on wondered if their work might lead to a new type of antibiotic to treat disease-causing bacteria. As they continued their studies, they instead discovered a powerful molecular tool that makes precise cuts in DNA at predetermined sites. This tool has revolutionized biological research, leading to drought and disease resistant crops, novel treatments and even the potential to cure certain genetic diseases.
3. The American Society of Human Genetics recently released a report detailing how human genetics and genomics research impacts the U.S. economy, society, and healthcare. In the United States, this field supports 850,000 jobs and generates $15.5 billion in tax revenue every year….that’s a higher dollar amount than the gross domestic profit of one-third of the countries in the world. The annual federal investment of more than $3 billion in human genetics and genomics has a return on investment of nearly five times that amount.
8. The plains zebra lives in the grasslands of south- ern and eastern Africa. This species of zebra can vary in the specific pattern of its stripes, including rare instances of spotting or nearly solid black across the torso. The genomes of 7 abnormally striped zebras were recently compared to 133 typically striped zebras
from nine locations. Zebras with abnormal striping showed increased levels of inbreeding. It is not known if altered stripe patterns are associated with health, ability to avoid predators or successfully reproduce.
More details can be found in the Shareable Science blogpost: How does genomics and genetics impact our world today?
4. An international consortium has analyzed the microbial communities of public transit systems from 60 cities around the globe. Samples were collected from railings, benches, ticket kiosks as well as the air. Over 4,200 species of urban microorganisms were identified, with 31 consistently appearing across almost all cities. Each city had its own combination of bacteria and viruses, primarily shaped by differences in climate and geography. Markers of antimicrobial resistance were widespread
HudsonAlpha faculty researcher Greg Barsh MD, PhD contributed to this work.
9. Thanks to new sequencing technologies, an updated and more complete giraffe genome was recently published. Comparing the giraffe genome to those fromother mammals, scientists found 500 genes unique to giraffes or containing DNA changes found only in giraffes. Interestingly, many were associated with growth and development, nervous and visual systems,
but present at relatively low levels. This type of map- ping gives public health officials a new set of tools to track potentially disease-causing microbes.
circadian rhythms, and blood pressure regulation, all areas in which the giraffe differs from its close rela- tives. These changes are associated with adaptations that allow giraffes to survive and thrive even with their unusually long body structure. More details can be found in the Shareable Science blogpost: Journeying into the giraffe genome.
HudsonAlpha faculty researcher Shawn Levy PhD contributed to this work.
5. Determining the pathways that convert typical cells to cancer is an important goal of cancer re- searchers. This involves identifying all the genes that drive tumor formation when mutated. By analyzing pub- licly-available cancer datasets, the Integrative OncoGenomics (IntOGen) pipeline classified 568 driver genes across 28,000 samples from 66 different cancer types. This includes 152 genes not previously designated as drivers of cancer. The next step is to understand why mutations that alter the function of these genes lead to abnormal cell growth and spread.
10. Aquabounty Technologies, Inc. has completed the first commercial scale harvest of its genetically engineered Atlantic salmon, sending 5 metric tons of the fish to commercial buyers. A one-time genetic modification made 30 years ago allows the salmon to reach market size in half the time. Sterile, female fish are raised in land-based tanks. Aquabounty salmon was approved by the FDA in 2015. The salmon have been sold in Canada since 2017.
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SCIENCE FOR LIFE
NEW FINDINGS
predicts the structure of human proteins
Proteins fold their string of amino acids into specific three-dimensional structures to carry out their biological function. Knowing that three- dimensional structure allows scientists to understand how the protein works, identify what goes wrong when it’s been altered and design medications to boost or silence its activity. Unfortunately, predicting protein structure is hard work and can take months of computer-based simulations and modeling. Less than ⅓ of all human proteins (collectively known as the proteome) have a known structure. DeepMind, a sister company to Google, is an artificial intelligence labo- ratory based in the UK. They developed AlphaFold2, a machine-learning platform that predicts protein structures with a very high degree of accuracy. The platform uses a repetitive system of model refinement, applied millions of times to improve predictions based on prior expe- riences. With a relatively high level of confidence, AlphaFold2 predict- ed structures for nearly the entire human proteome, as well as the proteome of 20 model organisms such as mouse, fruit fly and E. coli . DeepMind has predicted more than 350,000 protein structure and plans to submit up to 130 million more by the end of 2021, nearly half of all known proteins. Protein predictions are freely available and academic research teams can use AlphaFold2 at no charge. Even though these predictions must still be experimentally verified, the sudden availability of so many protein structures will likely transformmany aspects of biology and human health. REFERENCES: Tunyasuvunakool K. et al. Highly accurate protein structure prediction for the human proteome. Nature (2021) 596:590-596. DOI: 10.1038/s41586-021- 03828-1. And AlphaFold protein structure database: https://alphafold.ebi.ac.uk/
Long-read sequencing identifies “missed” disease-causing variants
Many neurodevelopmental diseases are genetic in nature. Despite advances in genome sequencing technology, specific diagnoses for these disorders remain elusive. This is likely because certain disease-causing genetic variants are challenging to detect with typical sequencing approaches. Traditionally, genome sequencing is performed by generating millions of “short” sequences, called reads, generally around 150 base pairs long. These short-reads are pieced back together like a puzzle using a human reference genome as a template. However, it is hard to accurately map certain types of short reads, especially regions containing highly repetitive stretches of DNA. These portions of the genome often go unanalyzed. One approach to overcome this limitation is to use a se- quencing platform that produces longer reads. “Long-read” sequencers generate sequences up to 1,000 times longer than short-read systems. Fewer, bigger puzzle pieces means fewer gaps in the assembled sequence. Greater genome coverage lets researchers and clinicians more accurately detect DNA variants. Recently, scientists used long-read sequencing to reanalyze the genomes of six families with children suspected of having a genetic neurodevelopmental disorder. The families had previously been sequenced using short-read technology, but no disease-causing genetic variant had been identified. Long-read sequencing found multiple genetic variants in each family that had previously been missed. Among these newly detected variants, disease-causing DNA changes were identified in two of the six children. If these findings are extended to larger populations, long-read sequencing may supplement or even replace short-read analysis pipelines, improving the rare disease genetic discovery rates. REFERENCE: Hiatt S.M. et al. Long-read genome sequencing for the molecular diagnosis of neurodevelopmental disorders. HGC Advances (2021) 2:100023. DOI: 10.1016/j.xhgg.2021.100023. The laboratories of HudsonAlpha faculty researchers Jane Grimwood PhD, Jeremy Schmutz and Greg Cooper PhD contributed to this work.
A replacement for karyotypes?
For over 50 years, clinicians have used photographs of stained chro- mosomes called karyotypes to identify chromosome duplications, deletions and large rearrangements associated with genetic disor- ders. Sometimes more precise methods of chromosome analysis such as FISH and CNV microarray have replaced karyotyping, but each ap- proach still has its limitations. However, a technology known as optical genome mapping may one day replace all three methods. Optical genome mapping begins by extracting DNA molecules hun- dreds of thousands of nucleotides long. These pieces are fluorescently labeled at commonly repeating DNA sequences and aligned into tiny nanochannels on a laboratory chip. Photographs are taken of the DNA fragments and the pattern of labels is identified and compared to a reference genome. Chromosome deletions, insertions, duplications and other abnormalities appear as changes in the pattern. In a series of head-to-head tests, optical genome mapping outper- formed karyotypes, FISH and CNV microarrays. Among a panel of 99 chromosomal variants often identified at birth, the tool correct- ly identified every alteration. It also scored well when identifying chromosome alterations linked to blood cancers that form over time. That said, more extensive validation is needed before this technology replaces existing detection methods. REFERENCES: Mantere T. et al. Optical genome mapping enables constitution- al chromosomal aberration detection. Am J Hum Genet (2021) 108:1409-1422. DOI: 10.1016/j.ajhg.2021.05.012. And Neveling K. et al. Next-generation cytogenetics: Com- prehensive assessment of 52 hematological malignancy genomes by optical genome mapping. Am J Hum Genet (2021) 108:1423-1435. DOI: 10.1016/j.ajhg.2021.06.001.
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Million year old genomes DNA has been isolated and sequenced from inside the teeth of three prehistoric mammoths, smashing the record for the
was the ancestor of the woolly mammoth. Earlier studies of woolly mammoth genomes had identified a set of genetic changes that likely allowed these animals to thrive in the frozen Arctic climate. Not surprisingly, the vast majority of these adaptive changes were already present in the DNA of the Siberian ancestors. The oldest tooth comes from a previously unknown branch of the mammoth family tree. The descendants of these mammoths ultimately migrated into North America. The data also implies the mammoth groups interbred at least a handful of times.
most ancient DNA ever analyzed. The molars were found in the Siberian permafrost, which helped preserve the DNA molecules. The samples are too old for carbon dating, so their ages were estimated using a combination of other approaches, including molecular dating of their mitochondrial DNA. The most recent of the mammoths lived more than 680,000 years ago, while the most ancient was estimated at 1.65 million years. The previous record for ancient DNA extraction was a horse that lived sometime between 560,000 and 780,000 years ago. Analysis of the samples suggests there were two different groups of mammoths living in Siberia during this timeframe. One population
REFERENCE: Van der Valk T. et al. Million- year-old DNA sheds light on the genomic his- tory of mammoths. Nature (2021) 591:265-269. DOI: 10.1038/s41586-021-03224-9.
Environmental DNA from air, land and sea
for thousands of years, meaning eDNA can be used to paint a portrait of ancient ecosystems. Several recent publications have recovered eDNA from the animal and human inhabitants of early communities and cave dwellings. One cave site in Spain contained Neanderthal nuclear and mi- tochondrial DNA frommultiple soil layers deposited 80,000 to 113,000 years ago.
Environmental DNA (eDNA) are trace amounts of DNA gathered indirectly from environmental samples rather than directly from an organism. Genetic material from the sample is amplified by polymerase chain reaction (PCR), followed by DNA sequenc- ing and analysis. Over the past twenty years, as sampling and sequencing technologies have become more sensitive, faster and cheaper, eDNA has been detected in water, ice cores, soil, sediment and even the air. Through a process known as eDNA metabarcoding, a single sample can provide a snapshot of an entire community or organisms. This makes eDNA a powerful tool for biodiversity inventory and monitoring. Because it can be applied to ancient as well as modern sites, it has growing applica- tions in paleobiology, archeology, conservation, wildlife trafficking and public health.
Air: Two recent papers describe vacuuming DNA from the air around zoos. Zoos are a useful location for a proof of concept study like this because they generally contain animals not found in the surrounding countryside. The snippets of captured DNA were amplified, sequenced and compared to those from a reference da- tabase. In each case, DNA was consistently identified from dozens of zoo animals. It’s unclear how much DNA floats off organisms into the air, how long those molecules remain aloft and how far they can travel. Those questions require further study.
Water: In the wild, eDNA’s ability to quanti- fy the number of individuals per identified species hadn’t previously been verified. In part, this was because the process requires catching and counting all the organisms in an ecosystem. Fortunately, a UK program aimed at eradicating an invasive freshwater fish species did exactly that. A set of fish ponds were drained and
all non-invasive fish were collect- ed, counted and placed in temporary holding ponds while the invasive species were killed. After the fish were returned to the original ponds, eDNA analysis was carried out and the
results were compared to the manually-collected data. All the fish species were identified and the total biomass of each species correlated closely with the eDNA findings. Separately, the eBioAtlas program announced plans to collect samples from 30,000 freshwater river systems around the globe over the next three years. The data from this $15M initiative will be used to identify freshwater species most at risk of extinction. Soil: Soil not only contains DNA frommicrobial organisms, but also genetic material that has been shed, excreted or decayed from larger organisms. These fragments of DNA can persist
REFERENCES: Di Muri C. et al. Read counts from environmental DNA (eDNA) metabarcoding reflect fish abundance and biomass in drained ponds. Metabarcoding
and Metagenomics (2020) 4: e56959. DOI: 10.3897/mbmg.4.56959. eBioAtlas — https://ebioatlas.org/ accessed 29 August 2021
Vernot B. et al. Unearthing Neanderthal population history using nuclear and mi- tochondrial DNA from cave sediments. Science (2021) 372:eabf1667. DOI: 10.1126/ science.abf1667. Lynggaard C. et al. Airborne environmental DNA for terrestrial vertebrate communi- ty monitoring. BioRxiv (2021) www.biorxiv.org/content/10.1101/2021.07.16.452634v1. Accessed 29 August 2021. Preprint. Clare E. et al. Measuring biodiversity from DNA in the air. BioRxiv (2021) www.biorxiv.org/content/10.1101/2021.07.15.452392v1. Accessed 29 August 2021. Preprint.
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SCIENCE FOR LIFE
NEW FINDINGS — AGRICULTURE
Genome of promising biofuel grass sequenced A lot of fuel is required to keep our country running. Americans use an average of 390 million gallons of motor gasoline and 197 million gallons of aviation gasoline, per day, to fuel planes, trains, and automobiles. Most of the fuel that we currently consume is fossil fuel formed from the fossilized, buried remains of plants and animals that lived millions of years ago.
USDA, EPA update biotechnology crop regulations
In America, crops developed with genetic technology are regulated by three federal agencies. The United States Department of Agriculture (USDA) oversees whether any genetically engineered (GE) plant poses a risk to become a plant pest in the environ- ment. The United States Environmental Protection Agency (EPA) regulates those GE plants that produce biochemicals used as pesticides. The Food and Drug Adminis- tration (FDA) ensures the safety and label- ing of all GE plant-derived food and feed. The USDA and the EPA modified their regulatory requirements in 2020, allow-
Fossil fuels are an exhaustible resource that will eventually run out. Burning fossil fuels can also have negative impacts on our environment through air and water pollution and the release of carbon dioxide, a known greenhouse gas thought to contribute to global warming. Biofuels are promising substitutes for fossil fuels that are produced from renewable, organic (carbon-containing) materials like plant matter and animal waste. These materials, termed biomass, include agricultural crops and agricultural waste, algae, dedicated energy crops, and forestry residues. Miscanthus grasses, which are used in gardens, paper production, and roofing, are a promising source of biomass. A team of researchers recently sequenced the full genome of an or- namental variety of miscanthus. The high-quality genome sequence will help researchers identify genes associated with traits of interest in miscanthus so they can breed or modify plants to improve certain processes such as biomass output and the ability to bounce back after winter. The genome sequence will also allow researchers to bet- ter understand other grasses that may be useful as biomass crops. REFERENCE: Mitros T. et al. Genome biology of the paleotetraploid perennial biomass crop Miscanthus, Nature Communications (2021) 11:5442. DOI: 10.1038/s41467- 020-18923-6. The laboratory of HudsonAlpha faculty researcher Kankshita Swaminathan PhD contributed to this work. Golden rice receives approval Vitamins and minerals are essential for healthy development, disease prevention, and wellbeing. Because most vitamins are not produced by the body, small amounts must be obtained from the diet. Vitamin A deficiency is the leading cause of preventable blindness in children and increases the risk of disease and death from severe infections such as diarrheal disease and measles. Low- and middle-income countries, whose diets are based mainly upon rice or other carbohy- drate-rich, micronutrient-poor calorie sources, bear the dispropor- tionate burden of vitamin A deficiencies. In the late 1990s, scientists developed a genetically modified rice, called golden rice, that could help combat vitamin A deficiency by providing consumers with beta-carotene their bodies could use to make vitamin A. Rice naturally possesses the components necessary to synthesize beta-carotene but the synthesis process is turned off in the edible rice grain. By introducing two genes into the rice, the pathway is turned on and beta-carotene accumulates in the grain. Studies have shown that one-cup of cooked golden rice provides 50 percent of the daily recommended allotment of vitamin A. Although golden rice has the potential to combat vitamin A deficiency, it just saw its first approval for use in 2020—almost two decades after it was first developed. The government of the Philippines announced that it was safe for consumption and could be planted for commercial use.
ing certain categories of GE plants to bypass the regulatory process if they met specific conditions. Previously, developers of GE crops had to undergo a lengthy approval process to show their products weren’t plant pests. Under the modified USDA regulations, plants created with biotechnology are exempt from regulatory approval if:
• the modified plants don’t pose a plant pest risk • conventional breeding techniques could have developed the same type of plant • the trait combinations are identical to previously-approved plants
The regulations also affirm that as long as there is no plant pest risk, crops developed using gene editing techniques will not require regulatory approval. The USDA has published a list of exempt plant-trait combinations, which developers can use to determine whether a new GE plant requires regulatory approv- al. Developers can also submit an “Am I Regulated?” request to the USDA for regulatory determination. Similarly, the EPA's updated rules state that plants engineered to produce pesticides are exempt from regulatory approval if they have a low-risk and could have been created using tradi- tional breeding approaches. Proponents note the new rules are based on decades of sci- entific research on agricultural biotechnology. They argue that streamlining the regulatory process reduces regulatory burdens for low-risk plants increasing the likelihood of innovation in new product development. However, some environmental and public health advocacy groups say the rules now leave most geneti- cally engineered plants unregulated by the USDA and the EPA, leaving consumers unaware of new biotech products. The new rules don’t affect the food safety oversight role of the FDA. REFERENCES: www.aphis.usda.gov/aphis/ourfocus/biotechnology/bio- tech-rule-revision/secure-rule/secure-about www.epa.gov/sites/production/files/2020-09/documents/10014-10- prepub-fr-doc-admin_esignature2020-08-31.pdf
REFERENCE: https://modernfarmer.com/2021/07/philippines-becomes-first-coun- try-to-approve-gmo-golden-rice/
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Human gene increases potato and rice output
Upcycling plastic into synthetic vanilla We live in a world filled with plastic. Unfortunately a large portion of the plastic that affords us daily convenienc- es and life-saving devices ends up in landfills and oceans across the world. In order to combat the growing environ- mental problem of global plastic waste, scientists have begun to pursue alterna- tive methods for recycling plastics. Most of the current methods degrade plastic and use the resulting base molecules to create more plastic materials.
Global population growth and reduced crop yield, due largely to increasing heat and drought, are putting a strain on the food supply throughout the world. For decades, scientists have been working to boost crop production but such processes are usually complicated, and often result only in small changes. In a recent study, scientists made a breakthrough that allows plants to yield more crops and withstand drought stress. A central concept in biology is that DNA is transcribed into RNA which is then translated into protein. Although gene expression is primarily controlled during the transcription of DNA to RNA, scientists discov- ered that it can also be regulated at the RNA level. Chemical markers placed onto RNA modulate which proteins are made and how many. The human FTO protein is the first known protein that erases these chemical marks on RNA. In humans and other animals, FTO is known to affect cell growth. Plants do not express an equivalent to human FTO. Inserting the gene that encodes FTO in both rice and potato plants increased their yield by 50 percent in field tests. The plants grew significantly larger, produced longer root systems, and were better able to withstand stress from drought. Scientists think that FTO controls a process known as m6A modifica- tion which places the chemical markers on RNA. FTO removes m6A marks from RNA to tone down some of the signals that tell plants to slow down and reduce growth. Without the signals telling the plants to slow their growth, the plants have a surge in crop yields. Although this process involves inserting a human gene into plants, scientists are working to discover how to get the same effect using the plant’s existing genome. REFERENCE: Yu Q. et al. RNA demethylation increases the yield and biomass of rice and potato plants in field trials, Nature Biotechnology (2021) DOI: 10.1038/s41587-021- 00982-9.
Scientists discovered a way to reap more value from the plastic recycling process by turning post-consumer plastic into synthetic vanilla flavoring. They used genetically engineered E. coli bacteria to convert terephthalic acid (a molecule derived from a type of plastic called PET) into the high value compound vanillin, which is the prima- ry component of extracted vanilla beans that is responsible for the characteristic vanilla smell and taste. Terephthalic acid and vanillin molecules look structurally similar. The genetically modified E. coli make a few changes to the number of hydrogen and oxygen atoms bonded to the terephthalic acid’s carbon ring, the circular structure in the center of the molecule. These chemical adjustments create vanillin. Further testing is needed to confirm the vanillin produced in this way is suitable for making fragrances and flavorings. The entire process also has to be successfully scaled to produce liters of vanillin. If that hurdle can be overcome, we’ll have a more environmentally friendly process to create this high-demand product.
REFERENCE: Sadler J. et al. Microbial synthesis of vanillin from waste poly(ethylene terephthalate), Green Chemistry (2021) 23(13): 4623-4904. DOI: 10.1039/d1gc00931a.
More details can be found in the Shareable Science blogpost: Upcycling plastic bottles into vanilla flavoring.
whitefly
are so successful at feasting on plants because their genome contains a plant gene that protects the insects from phenolic glycosides, toxins that many plants produce to defend themselves against such pests. This is the first known example of natural gene transfer from a plant to an insect. Scientists think that a virus possibly shuttled genetic material from the plant into the whitefly genome. After the scientists discovered the gene and confirmed it came from plants, they decided to see if inactivating it removed the whitefly's protective edge. The team engineered tomato plants to produce a double-stranded RNA molecule capable of shutting down expression of the gene. Nearly all of the whiteflies that fed on these tomato plants died. With this discovery, scientists can develop crops that are resistant to the whiteflies but that will not cause new harm to other species. REFERENCE: Xia J. et al. Whitefly hijacks a plant detoxification gene that neutral- izes plant toxins, Cell (2021) 184:1693-1705. DOI: 10.1016/j.cell.2021.02.014.
Insect incorporates plant gene to avoid plant defenses
During their 400 million year evolution with their insect foes, plants developed specialized defenses to protect themselves. Whiteflies, a close relative to aphids, are among the most de- structive plant pests, circumventing the defenses of hundreds of types of plants. They drink sap from the plants and excrete a sticky, sweet substance called honeydew that serves as a breeding ground for mold. Whiteflies are also carriers for more than 100 pathogenic plant viruses. Scientists set out to determine how whiteflies manage to evade the defenses of so many plants. They discovered that whiteflies
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SCIENCE FOR LIFE
NEW FINDINGS — BACTERIA AND VIRUSES
Genetic clues from the 1918 influenza pandemic Although the 1918-19 flu pandemic spread around the globe in three different waves, the second and third were much deadlier than the first. An analysis of viral RNA from preserved patient tissue may bring us closer to understanding how the virus became more lethal.
immune response. First wave samples were more similar to influenza sequences from birds, where the virus is thought to have originated. This suggests the virus gained mutations in this gene between the first and second wave, allowing it to better evade the early immune response and spread unchallenged. The third German sample contained changes in genes for the poly- merase complex, which makes copies of the viral genome as part of the infection process. The altered copying complex was recreated in laboratory cells (no other part of the virus was reproduced). The complex was only half as active as the copying proteins from later viral strains. While it’s difficult to compare controlled lab experiments to real-world human infections, this data hints that early versions of the virus were less efficient at reproducing inside humans. This also may have contributed to the milder first wave. REFERENCE: Patroro L.V. et al. Archival influenza virus genomes from Europe reveal genomic and phenotypic variability during the 1918 pandemic. BioRxiv (2021) https://www.biorxiv.org/content/10.1101/2021.05.14.444134v1. Accessed 28 August 2021. Preprint. vaccines. The Centers for Disease Control’s national SARS-CoV-2 genomic surveillance program (https://covid.cdc.gov/covid-da- ta-tracker/#variant-proportions) identifies and tracks variants circulating in the United States. The human genome has also been a focus of pandemic-related health research, searching for genetic changes that impact our immune response to viral infection. The COVID-19 Host Genetics Initiative analyzed genetic markers from nearly 50,000 COVID-19 patients and 2 million controls across 19 countries. Thirteen regions of the genome were associated with susceptibility to infection or severe illness. Nine of those regions contain biologi- cally plausible genes, several linked to immune function or genes normally expressed in the lungs.
influenza virus
Viral RNA was extracted and sequenced from preserved museum samples of lung tissue collected throughout Germany during 1918- 19. Three were positive for the influenza A strain and two of these were definitively dated to the milder first wave. These were compared to previously sequenced samples from later waves. Several changes were observed in a gene that helps the virus evade the body’s initial
Genomic studies and COVID-19 Genetic tools have been critical to help scientists understand and respond to the COVID-19 pandemic. Genomic sequencing first determined the SARS-CoV-2 virus was responsible for the unidentified cluster of respiratory infections in the Wuhan prov- ince of China. Scientists sequenced genetic material from patient samples and analyzed the non-human genetic fragments. They determined a new member of the coronavirus family was causing the infection. Early studies also found the genetic recipe of the novel virus was very similar to bat coronaviruses, suggesting the virus likely originated in bats. Once laboratories knew the genetic sequence, they could develop tests to diagnose infections. These tests use a technology called polymerase chain reaction (PCR) to detect small amounts of genetic material from the virus. PCR-based tests are the gold standard for diagnosing COVID-19. To reduce costs and maximize impact, some labs combine small amounts of individual patient samples into a single pool. If the pool tests negative, all samples are virus free. If the pool tests positive, researchers test each of the initial samples to determine which contains the virus. A modified version of PCR testing can detect the virus in waste- water samples. This gives college campuses, hospitals, and neighborhoods an important early detection tool. A small fraction of virus samples from patients undergo a genomic "deep dive" to track how the virus changes over time. A worldwide network of labs scans these viral genomes for changes in the genetic recipe (also called variants or mutations). All viruses undergo these modifications over time. Most are un- important, but some alter how the virus infects people or how ill it can make patients. Viral sequencing lets public health experts track the spread of different strains. The alpha, beta, and delta variants are examples of these changes. Researchers then de- termine if the strains are more or less transmissible, have a dif- ferent risk of serious illness, and respond to current treatments/
HudsonAlpha has a number of educational resources related to the COVID-19 pandemic. The initial sequencing of the SARS-CoV-2 virus is discussed in the Shareable Science blogpost The Genetics of Coronavirus. The process of genomic surveillance is explained in the Everyday DNA blogpost Genomic surveillance: using the genome to track and monitor viruses. Lastly, there are more than 70 COVID-specific videos on the Shareable Science beyond the blog site.
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NEW FINDINGS — INFECTIOUS DISEASE
Gut microbes coordinate immune responses in mice
Most animals follow 24 hour circadian patterns, with periods of activity followed by times of rest. Mealtimes follow these patterns, with people generally eating during the day while animals like mice eat primarily at night. Inside the intestines of many animals, microbes synchronize their own activity to match the feeding patterns of their host and availability of nutrients. A recent study suggests that in mice this synchronization sig- nals the immune system to be on the alert for harmful bacteria hitching a ride on the most recent meal. Researchers began by tracking the levels of REG3G, an antimicrobial protein mice secrete from their small intestines. Levels peaked at night, when the mice were feeding. Intrigu- ingly, protein levels were consistently low in mice lacking a gut microbiome, suggesting a connection between intestinal bacteria and the antimicrobials. When scientists looked for cyclical patterns among gut microbes, they discovered that segmented filamentous bacteria attached to the lining of mice intestines each night, presumably to extract nutrients from the forthcoming feeding.
A spacey new bacteria As part of an ongoing microbial tracking and sequencing experiment, environmental samples from the International Space Station have identified a previously unknown species of bacteria closely related to Methylobacterium. Earth-bound methylobacterium species, often found in soil and freshwater, are gram negative, rod-shaped bacteria involved in nitrogen fixation, protecting against plant pathogens, and promoting plant growth. The discovery of novel plant-associated bac- teria on the ISS is perhaps not surprising as ISS astronauts have been growing small amounts of food on the station for years. Researchers suspect the novel bacteria may be derived from bacterial strains often associated with rice that may have hitched a ride to the space station with either a seed or a food shipment. This discovery could prove valuable as microbes that promote plant growth are critically import- ant for long-term human space exploration. They may play a future role in keeping plants healthy for oxygen and food production under the extreme conditions of long-term space travel and colonization. REFERENCE: Bijlani S. et al. Methylobacterium ajmalii sp. Nov., Isolated From the International Space Station. Frontiers in Microbiology (2021) 12:639396. DOI: 10.3389/ ficb.2021.639396. Microbiome-friendly food benefits undernourished children New research has uncovered a potential link between the gut bacteria of malnourished children and their ability to recover from the effects of starvation. Using fecal samples, researchers had previously com- pared the intestinal microbiome of healthy children to those suffering frommoderate to severe malnutrition, noting the gut biomes of un- dernourished children appeared 'stunted' in development. When gut microbes from undernourished children were transferred to mice, the mice developed metabolic dysfunctions. Like the children, the mice broke down amino acids for energy rather than sugars and their rate of weight gain and bone growth slowed. In a follow-on small human clinical trial, researchers monitored 118 children under age 2 who had moderate malnutrition. Half received the standard calorie-dense supplemental food. The other half received a different supplement containing foods selected to nourish the gut microbiome. Both supplemental foods used locally available ingredients, a critical feature for long-term implementation. Even though the microbiota-directed food regime contained fewer total calories, those children gained more weight and grew more rapidly than the group receiving the standard food supplement. The microbi- ome-nourished children also had increased levels of blood proteins associated with bone growth and brain development. Follow up studies are needed to determine if these short-term gains offset the effects of early life malnutrition. REFERENCE: Chen R.Y. et al. A Microbiota-Directed Food Intervention for Undernourished Children. New Engl J Med (2021) 384:1517-1528. DOI: 10.1056/NEJ- Moa2023294.
Through a series of experiments, the research team deter- mined that this bacterial attachment activates a host immune response designed to heal the bacterial damage to the lining of the gut. Secreting REG3G is part of this response. The REG3G helps neutralize any foreign bacteria present in the food, and serves as the first line of defense against food-based infection. This is the first time gut microbiota have been clearly linked to the innate immune response. The mouse gut uses bacterial behavior to anticipate the 'riskiest' time of day and prepare the immune defense. From a resource perspective, it’s costly to produce antimicrobial molecules. Cellular energy can be saved by making them only when they are likely to be needed. It is unclear if similar relationships exist for human intestinal/ immune interactions. The researchers note that chronic sleep disruption in people is tied to increased susceptibility to infec- tion. Segmented filamentous bacteria do attach to the human gut lining, but it is not known if attachment follows a circadian cycle. If humans do have a connection between gut microbiome and immune response, that knowledge may reshape the deliv- ery and timing of antibiotics, vaccines and immune-modulating medications. REFERENCE: Brooks II J.F. et al. The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock. Cell (2021) 184:P4145-4167.E12 DOI: 10.1016/j.cell.2021.07.001.
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SCIENCE FOR LIFE
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