Biotechnology Discoveries and Applications for the Extension to high school science curriculum.
2025 GUIDEBOOK CONTENTS
About HudsonAlpha Institute for Biotechnology ........................................... 2–3 Executive Summary ................................................................................................ 4 Science Snapshots .................................................................................................. 5 New Findings ..................................................................................................... 6–15
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.
Pangenomes in Genomic Research ..............................................................16–17 HudsonAlpha Life Science Educator Resources ............................................18–19 HudsonAlpha Student Opportunities .............................................................20–21 HudsonAlpha Digital Application Resources .................................................... 22 Community Resources ......................................................................................... 23 Alabama Course of Study Alignment .......................................................... 24-28 Snapshot References and Image Credits .......................................................... 29
ONLINE EDUCATOR RESOURCE HUB The HudsonAlpha Educator Resource Hub is your one-stop shop for supporting materials, some devel- oped 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. Learn more at hudsonalpha.org/educatorhub
About HudsonAlpha Institute for Biotechnology
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, and economic development to improve the human condition around the globe.
The state-of-the-art facilities co-locate nonprofit scientific researchers with entrepreneurs and educators. HudsonAlpha has become an international leader in genetics and genomics research and biotech education. HudsonAlpha is supported by grants from the U.S. federal government, the state of Alabama, private foundations, and philanthropic contributions.
Genomic Research
HudsonAlpha scientists are adding to the world’s body of knowledge about the basis of life, health, disease and biodiversity and seeking to enable: ● Earlier and/or less invasive diagnostics ● Better, more customized treatments for disease ● Improved food, fiber and energy sources
Current research focus areas are: Foundational Research
Significant Research Publications
Plant Genetics Applying genomic knowledge to improve the quality and sustainability of our food, fiber, and fuel production, and our environment's health.
Human 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 understanding of biological phenomena. Includes studies of natural variation, principles of bioethics, and computational biology and bioinformatics
Our researchers have authored more than 1,100 scientific publications since HudsonAlpha opened in 2008 to help secure a global leadership position in genomic research.
hudsonalpha.org/research
2
Educational Outreach
hudsonalpha.org/education
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, and the community through hands-on classroom modules, in-depth school and workshop experiences along with digital learning opportunities. HudsonAlpha also provides educational opportu- nities for healthcare providers for patients who are making medical decisions using personal genomic information.
OVER THE LAST 16 YEARS
more than
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, summer camps, 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 developed kits and activities provide engaging hands-on learning experiences in genomics and biotechnology. Activities are developed for elementary, middle, and high school student audiences and aligned to both state and national life science curriculum. HudsonAlpha’s kits are distributed across Alabama through partnerships with the Alabama Math, Science and Technology Initiative and Alabama Science in Motion and are also available worldwide through Carolina Biological.
Clinical Education HudsonAlpha is empowers patients to be informed genomic healthcare consumers and members of society. Our genetic counselors provide 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. The Huntsville 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.
hudsonalpha.org/innovate
HudsonAlpha is growing in the Wiregrass area in downtown Dothan to bring agriscience innovations, new area jobs and economic opportunities to the region. The expansion is sparking innovative research, fostering STEM education and inspiring economic growth. hudsonalpha.org/wiregrass
3
EXECUTIVE SUMMARY
Welcome to the 2025 Annual Biotechnology Guidebook! Whether you’ve been with us since the first edition in 2010 or you’re discovering the Guidebook for the first time this year, I’m thrilled to have you here. Through the pages that follow, I’ll share some of the most exciting breakthroughs in genomics and biotechnology from the past year. Selecting stories for the Guidebook becomes more challenging each year as the pace of discovery accelerates, driven by the availability of vast datasets, advanced computational tools, and global collaboration across institutions and borders. In the following pages, you’ll explore: l How ancient DNA from preserved samples helped reconstruct the genome of the woolly mammoth and victims of the Mt. Vesuvius eruption in 79 AD. l The groundbreaking work on microRNA that earned a Nobel Prize in Physiology or Medicine, 40 years after its discovery. l The powerful role of artificial intelligence in accelerating genomic discoveries. l The FDA approval of a new drug targeting amyloid plaques in Alzheimer’s disease. l A fascinating type of mouth bacteria capable of dividing into 14 new cells at once. l The impact of long-read genome sequencing in providing answers for more patients with rare genetic diseases than ever before. Educators can use this Guidebook to bring the latest advancements, far too recent for textbooks, into their classrooms. It connects the "why" and the "wow" of life science, enhancing curricula with fresh, real-world stories. But the Guidebook is just one way HudsonAlpha engages with educators. We invite middle and high school life science educators to explore the HudsonAlpha Educator Resource Hub and our suite of hands-on kits, available worldwide through our partnership with Carolina Biological. Additionally, we offer numerous one-day and week-long professional development workshops throughout the year. We're particularly excited to share our latest hands-on activity, How do Polygenic Risk Scores Stack Up, which recently won a “Best in STEM” award. This activity allows learners to delve into polygenic risk scores—a method for quantifying disease risk based on multiple genetic factors. Our mission at HudsonAlpha Educational Outreach is to inspire and prepare the bioscience workforce of tomorrow while fostering a genomically-literate community. This Guidebook is just one of many ways we work towards that goal. There is so much incredible work happening in the fields of genomics and biotechnology. The stories we’ve selected for this Guidebook represent only a glimpse of the remarkable achievements from the past year. I hope you enjoy reading these stories as much as I enjoyed finding and writing about them; and that it leaves you wanting to go and learn more.
Kelly East
This Guidebook would not be possible without the team of HudsonAlpha writers, reviewers, and designer who helped ensure this year’s edition was both readable and visually compelling. I want to extend a huge thank you to Madelene Loftin, Marquasha Carter, Meagan Cochran, Tanner Coleman, Jennifer Hutchison, Whitley Kelley, Nikki Mertz, Malcolm Parker, April Reis, Sarah Sharman, Cathleen Shaw, and Aubri Simpkins.
Kelly East, MS, CGC Vice President for Educational Outreach HudsonAlpha Institute for Biotechnology email: keast@hudsonalpha.org
4
SCIENCE SNAPSHOTS a quick summary of 10 genetics and biotech stories
6. Blueberries contain anthocyanin, a pigment that should make their skin appear dark red. Instead, the fruit appears blue because tiny structures in their waxy coating reflect blue and ultraviolet light. This effect, called structural coloration, differs from pigmentation and is also seen in other fruits like grapes and some plums, giving them their iconic blue hues. 7. Fat cells retain an epigenetic memory of obesity, contributing to the yo-yo effect in diet and weight loss. Researchers found characteristic epigenetic changes in the nucleus of fat cells that persisted after weight loss, making it easier for those cells to return to an over- weight state. 8. Genome sequencing of the fork fern has set a new record for genome size among eukaryotic organisms. At an enormous 160 billion base pairs (160.45 Gbps), its genome is over 50 times larger than the human genome. Understanding the mechanisms that control genome size could offer valuable insights into evolutionary processes and biodiversity. 9. Tongue color has traditionally been used in Chinese medicine to diagnose conditions like diabetes, asthma, and kidney failure. Recently, researchers developed and tested a machine learning algorithm to analyze tongue images,
1. Learning is often associated with complex nervous systems, but even single-celled organisms show signs of learning through habitation. Habituation is a decreasing response to repeated exposure over time. How do simple cells with no brain exhibit this complex behavior? Researchers have discovered molecular networks in single cells that capture and store environmental information, acting as a simple form of memory. 2. A Bengal cat's "glitter coat" is not due to actual glitter but a unique trait in its fur that makes it appear shiny. A recent study on the Bengal cat genome identified that the glittery coat is caused by a change in the Fgfr2 gene, which plays a key role in embryonic development. While a complete loss of Fgfr2 is lethal, a moderate reduction in gene expression results in the desirable glittery coat.
The laboratory of HudsonAlpha faculty researcher Greg Barsh, MD, PhD, contributed to this work.
3. In 79 CE, Mount Vesuvius erupted, burying Pompeii under ash. The packed ash
Bengal cat'
preserved human victims’ shapes, allowing excavators to create plaster molds and make guesses about their genders and relationships to one another. Recent DNA analysis of bone fragments has revealed new information, challenging these previous assumptions.
classify their color, and predict diseases. The AI tool successfully distinguished between the tongues of healthy and diseased people with over 95% accuracy.
4. A recent study explored the microbial make- up of microwave ovens and found interesting differences between home microwaves and those found in scientific laboratories. At home, micro- waves are teeming with the same types of bacteria that are found on human skin and other kitchen surfaces, while laboratory microwaves host tougher bacteria that can survive intense heat and radiation. These findings provide insights into how environments shape microbiomes. 5. Scientists uncovered a tail-tale sign of our evolutionary past. A small insertion of genetic material has been linked to the loss of tails in ancient hominoids. While this change may have helped our ancestors walk upright, it also appears to have created a risk for neural tube defects, revealing an evolutionary trade-off.
10. A 52,000-year-old woolly mammoth skin sample revealed its 3D genome structure. The jerky-like, dehydrated state preserved its DNA by preventing fragmentation and halting molecular activ- ity. The ancient mammoth had 28 chromosome pairs, with gene organization similar to the Asian elephant. This discovery sparks curiosity about what other pre- served tissues might lie hidden in the Arctic, waiting to tell new stories about Earth’s history.
5
SCIENCE FOR LIFE
NEW FINDINGS — GENETICS AND GENOMICS
An Ancient Appetite
Enzymes are essential for digestion, breaking down
complex foods into smaller, usable molecules. Amylase, an enzyme pro- duced in saliva and the pancreas, converts dietary starches into sugars. The gene AMY1 encodes salivary amylase. AMY1 genes are clustered on chromosome 1, a region prone to DNA duplication and rearrangement. The number of AMY1 copies varies widely among individuals and has increased over time. Scientists have long hypothesized that rising AMY1 gene copies align with our transition to agriculture and starch-rich diets. However, studying this region has been difficult due to its repetitive structure. Using advanced technologies like long-read sequencing and optical genome mapping, researchers analyzed 98 modern genomes, uncovering 30 unique versions of the amylase region. They found the number of AMY1 gene copies ranged from 2 to 16 per person. Ancient DNA analysis revealed that multiple AMY1 gene copies existed long before agriculture. The 45,000-year-old Ust’-Ishim man had six copies, and some Neanderthals had three. While initial gene duplications occurred before humans split from Neanderthals, copy numbers rose significantly after farming began. Neolithic humans had fewer copies than post-agricultural populations, highlighting adaptation to starch-heavy diets. This research highlights the dynamic relationship between the human genome and environment and may lead to further understanding of individual variations in metabolism and diet. n
Old Genes, New Mice Stem cells can develop into many different types of cells in multicellular organisms. They have the unique ability to divide and differentiate into specialized cell types, which is important for embryonic development, as well as growth and tissue repair throughout an organism’s life. Understanding stem cell biology is important because it could help explain how some diseases develop and how to best treat them. In a ground-breaking effort, researchers have recreated mouse stem cells using genes from choanoflagellates, single-celled organ- isms considered the closest living relatives of animals. They have ancient versions of Sox and POU genes, which control a stem cell’s ability to differentiate into other types of cells, a phenomenon called pluripotency. While it is peculiar that a single-celled organism would have genes for cell differentiation, the researchers were able to leverage it in their experiments. They replaced an essential gene ( Sox2 ) in mouse cells with the ancient version from choanoflagellates, successfully reprogram- ming them into stem cells. The modified stem cells were injected into developing mouse embryos. The resulting mice displayed traits from both the embryo and the newly introduced engineered cells, confirming the ancient gene’s functional role in pluripotency. This discovery challenges the idea that genes responsible for cell differentiation evolved exclusively within animals. This experiment revealed that genetic tools for stem cell formation were already present in unicellular ancestors long before multicellular life. These genes functioned remarkably similarly across a billion years of evolution, which shows the flexibility of genetic mechanisms and how they are recycled for new functions during evolution. The research has impacts beyond a better understanding of the mechanisms of evolution. It also paves the way for new biotechnology tools where manufactured forms of Sox and POU genes might perform better than their natural counterparts. A better understanding of stem cell formation could lead to new therapies and reprogramming cells to treat disease or repair cell damage. n
REFERENCE: Yilmaz F, et al., Reconstruction of the human amylase locus reveals ancient duplications seeding modern-day variation. Science . [2024] 386{6724):eadn0609. https://www.science.org/doi/10.1126/science.adn0609?urlver=Z39.88-2003&r- fr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
REFERENCE: "Scientists recreate mouse from gene older than animal life." ScienceDaily , 18 November 2024. Accessed 14 January 2025. https://www.sciencedaily. com/releases/2024/11/ 241118125716.htm
6
Breaking Down Meiosis During meiosis, gametes (egg and sperm cells) are formed, each containing half of the parent’s genetic material. During this process, homologous chromosomes exchange segments of DNA, a process known as crossing-over. This recombination is essential for genetic diversity and proper chromosome movement. Recombination begins with programmed DNA double-stranded breaks (DSBs). Some breaks are repaired without crossover using the identical sister chromatid as a template, while others use the homologous chromosome, leading to genetic variation. Recent research shows that DSB repair is more error-prone than previously believed, contributing to genetic variation across generations. Notably, DSBs during meiosis result in new genetic changes in 1 in 4 sperm and 1 in 12 eggs. Researchers also discovered that DSBs are often concentrated in specific regions of the genome, known as “recombination hotspots.” A repaired DSB is significantly more likely to result in mutations, such as single base pair changes or structural variants, compared to areas without DSBs. The study also found that DSB repair is less accurate in males, correlating with a higher mutation rate observed in sperm.
This study highlights that the DNA break and repair process during meiosis is a major source of genetic change in the human germline. While meiotic recombination is critical for genetic diversity, it comes with an increased risk of introducing new DNA changes. While many DNA changes have little to no impact, some can have a significant impact on health and disease risk. n
REFERENCE: Hinch R, et al., Meiotic DNA breaks drive multifaceted mutagenesis in the human germ line. Science . [2023] 382(6674):eadh2531. Epub 2023 Dec 1. https://www.science.org/doi/10.1126/science.adh2531
AI Driven Discovery Every cell in an organism’s body contains a complete set of genetic instructions, but only certain genes are active in each cell. This precise control is essential for creating the diverse cells in each organism. Cis-regulatory elements (CREs) are DNA sequences that act like switches, determining which genes are turned on or off in particular cells. The human genome has many highly specific CREs, each with distinct features that target certain genes or cell types. Researchers are using AI to understand those features and design new CREs. Researchers selected hundreds of thousands of DNA sequences and cataloged their CRE activity in three different cell types. This data was used to train an AI model to find patterns and predict which specific features in CREs impact expression across different genes and cell types. The researchers used the model to design a platform called Computational Optimization of DNA Activity, or CODA, which creates synthetic CREs designed to target specific genes or cell types. When the synthetic CREs were tested on cells, researchers were surprised to find they were less likely to affect unintended cell types than naturally occurring CREs. Finally, the team tested the synthetic CREs on zebrafish and mice, showing genes could be regulated in brain or liver cells without affecting expression in the rest of the animal. This exciting breakthrough illustrates how AI can help discover the functions of complicated DNA sequences. Although more study is needed, synthetic CREs might also provide a way to treat disease through controlling gene expression. n REFERENCE: Gosai SJ, et al., Machine-guided design of cell-type-targeting cis-regulatory elements. Nature. [2024] 634:1211–1220 https://doi.org/10.1038/s41586-024-08070-z
A Nobel Prize 40 Years in the Making
Victor Ambros and Gary Ruvkun were awarded the 2024 Nobel Prize in
Physiology or Medicine for their groundbreaking work on microRNAs and gene expression, which they began in the 1980s. As post-doctoral fellows studying cell and tissue development in the roundworm C. elegans , they discovered that the gene lin-4 suppressed the expression of another gene, lin-14 . Years later, while leading their own research labs, they collaborated and uncovered the mechanism behind this interaction. They found that the lin-4 gene produces short RNA segments, just 22 bases long, which are not translated into proteins. These ultra-short RNA molecules, now known as microRNAs (miRNAs), have sequences complementary to the messenger (mRNA) of lin-14 , allowing them to bind and prevent the lin-14 mRNA from being translated into protein. This discovery explained how lin-4 regulates the expres- sion of lin-14 . Ruvkun’s subsequent discovery of another microRNA demonstrated that miRNAs are not unique to roundworms but are present in various animals. The molecule discovered by Ambros and Ruvkun was tiny, but the impact was large. Further research into microRNAs has discovered roles for these tiny sequences in many developmental and disease pathways. n REFERENCE: “The Nobel Prize in Physiology or Medicine 2024” The National Assembly at Karolinska Instituet. 18 December 2024. https://www.nobelprize.org/prizes/medicine/2024/press-release Accessed 14 January 2025. Press Release.
7
SCIENCE FOR LIFE
NEW FINDINGS — AGRICULTURE
The Pearfect Genome Assembling and annotating the genomes of key crop species provides invaluable insights into the genes responsible for various traits. This process
Boosting Plant Growth Scientists researching plants for bioenergy have made a genetic discovery that could have wide-reaching effects. They identified a gene called Booster in the blackwood cotton tree, a fast-growing species in the poplar family. Trees with the naturally occurring Booster gene produced more rubisco (RBCU), the protein responsible for converting carbon dioxide into glucose during photosynthesis. This gene significantly enhanced the rate of photosynthesis, leading to faster growth and increased height. When the Booster gene was inserted into Arabidopsis plants, they had up to 62% more rubisco and grew dramatically taller. This discovery has far-reaching implications. The Booster gene could enhance photosynthesis and increase output across a variety of food crops, offering multiple benefits with a single genetic modification. Unlike previous changes that were species-specific, this gene could work across different plants. What makes the Booster gene discovery even more fascinating is its origin. It’s a chimeric gene formed by the fusion of genes from three different sources. One source is the RBCU gene, which codes for rubisco and is present in all green plants. Another source for the Booster gene is a bacte- rium that inhabits the roots of poplars, and the final source is an ant that interacts with a poplar bark fungus. The chimeric Booster gene, the result of lateral gene transfer, has been preserved in poplars for millennia. Experts previously considered such chimeric genes to be evolutionary remnants with no function, making the discovery of a func- tional gene from this fusion even more surprising. n REFERENCE: Biruk, A., et al. An orphan gene BOOSTER enhances photosynthet- ic efficiency and plant productivity. Developmental Cell (2024). 1534-5807. https://doi.org/10.1016/j.devcel.2024.11.002
enables genome-assisted breeding, allowing breeders to leverage molecular data to make informed decisions and speeding up the incor- poration of desirable traits into new cultivars. Accelerated crop breeding is increasingly important in an ever- changing world with a growing population. Pears are a highly valued fruit in today’s economy. In 2021, pear production in the United States was valued at $353 million. Over the past decade, several pear genomes have been sequenced and assembled, but these efforts lacked the ability to separate sequences by their parent of origin, as they could not be phased. Recent advancements by scientists at the HudsonAlpha Institute for Biotechnology, in collaboration with students from Auburn Univer- sity, have resulted in a chromosome-scale, phased assembly of the d’Anjou pear genome. This work was part of the American Campus Tree Genome (ACTG) initiative, where students actively participated in assembling, annotating, and publishing a reference genome for this economically significant species. The completed d’Anjou genome sequence spans 540 million base pairs and consists of all 17 chromosomes. This new, detailed genome data has uncovered thousands of structural genomic variations that may be linked to important traits. Notably, the sequence revealed a whole genome duplication event, a characteristic shared by both pears and apples. These new genomic discoveries hold great poten- tial for informing future breeding strategies, helping to improve the quality, yield, and resilience of pear cultivars, and accelerating the development of varieties with enhanced traits to meet the needs of both producers and consumers. n REFERENCE: Yocca, A., et al. A chromosome-scale assembly for ‘d’Anjou’ pear, G3 Genes|Genomes|Genetics, Volume 14, Issue 3, March 2024. https://doi.org/10.1093/g3journal/jkae003 The laboratory of HudsonAlpha faculty researcher Alex Harkess, PhD, contributed to this work.
Molecular Farming for Swine-Flavored Soy
It leverages existing agricultural practices and infrastructure, allowing animal proteins to be harvested using traditional farming methods, with plants
Molecular farming is an innovative approach that uses plants or microbes to produce protein products traditionally derived from animals. Unlike other meat substitutes, such as the Impossible Burger ™ — which uses genetically engineered yeast to produce beef heme proteins for a meat-like flavor — molecular farming involves integrating animal protein production directly into plants. Scientists at the company Moolec Science™ have used molecular farming to develop a modified soy plant that they have named “Piggy Sooy.” The plant has pig genes integrated into its DNA that redirect the plant’s protein synthesis machin- ery to create and accumulate pig myoglobin rather than the soy leghemoglobin protein. Pig myoglobin is similar in structure to leghemoglobin but gives meat its pink color and distinct flavor. The genetic modifications result in soybeans with a pink hue and mild, meaty taste. According to Moolec, molecular farming offers several advantages beyond enhancing the taste of plant-based meats.
acting as biological factories powered by photosynthesis. This approach also has potential applications in producing protein-based drugs and other valuable products, presenting exciting opportunities for sustainable biotechnology. In 2024, the “Piggy Sooy” plant reached a major milestone by receiving USDA approval for production in the United States. This approval allows for the cultivation and transportation of these genetically engineered soybeans without additional permits, as they pose no greater pest risk than non-engineered soybeans. n REFERENCE: U.S. Department of Agriculture, Animal and Plant Health Inspection Service. ([2024]). Response Letter Regarding Regulatory Status Review of soybean developed using genetic engineering for accumulation of a meat protein (Document ID: [23-234-01rsr]). [Riverdale, MD]: APHIS. https://www.aphis.usda.gov/sites/default/files/23-234-01rsr-response.pdf
8
Sugarcane’s Complicated Genome Sequencing plant genomes is notoriously difficult. Plants have tough cell walls that complicate DNA extraction, and many plants produce compounds that can contaminate samples. Additionally, plant genomes are massive, often far larger than the human genome, and filled with repetitive DNA sequences that make genome assembly difficult. Many plants are also polyploid, with multiple copies of each chromosome. This makes it challenging to determine where each DNA sequence belongs within the genome. Despite the challenges, studying plant genomes is crucial for two key reasons: understanding how plant species are related and identifying the genetic changes that contribute to desirable and harmful traits. Sugarcane ( Saccharum officinarum ), the world’s most harvested crop by weight, is a vital source of sugar, biofuel, and biomaterials. However, its complex genetic makeup has long hindered the creation of a high-quality reference genome. This complexity stems from its massive genome size (12 copies of each chromosome, more than 100 chromosomes per cell) and large amounts of repetitive DNA. Recent work by scientists at the HudsonAlpha Institute for Biotechnology and the Department of Energy Joint Genome Institute finally made a high-quality sugarcane reference genome possible. Using advanced sequencing techniques, they successfully tackled the challenges of the sugarcane genome and assembled a high-quality genome for the sugarcane variety known as R570. The use of long-read sequencing was critical, allowing researchers to capture longer DNA fragments and more easily piece together overlapping sequences. Parkinson’s and Pesticides Parkinson’s disease (PD) is a progressive neurological disorder caused by the build-up of misfolded alpha-synuclein particles in brain cells. The clumps of alpha-synuclein, known as Lewy bodies, disrupt nerve cell function and lead to the muscle tremors commonly seen in patients with PD. As the U.S. population ages, the incidence of this common neurodegenerative disorder is rising. PD is a multifactorial condition influenced by a mix of genetic and environmental factors. While rare familial cases that are linked to single genetic changes occur, most PD cases result from multiple interacting risk factors. Research has long suggested a link between pesticide exposure and Parkinson’s Disease (PD) risk. However, exposure alone does not guarantee the development of PD, as some exposed individuals never develop the disease, while others do so without pesticide contact. A recent study analyzed genetic data from patients with PD who were exposed to pesticides for a long time, especially those used on cotton. This study identified genetic variants that may account for differences in disease risk. Notably, 26 of the genes with identified variation are related to lysosome function. Lysosomes are organelles that break down dam- aged proteins and recycle cellular components through a process
called autophagy. Scientists propose that lysosomal dysfunction in clearing misfolded alpha-synuclein could start the formation of Lewy bodies and, ultimately, the onset of PD. The study also revealed that combining genetic risk variants
with pesticide exposure may amplify the risk of lysosomal failure.
This interplay highlights the importance of studying environmental
triggers alongside genetic predispositions. Most of the genetic variants identified would only cause minor changes in lysosomal function and
not lead to disease on their own. However, when combined with prolonged pesticide exposure, the risk of lysosome failure and development of PD is significantly higher. This study provides new insights into complex gene-environment interactions and could open up new potential treatment pathways for Parkinson’s disease. n REFERENCE: Ngo, K.J., et al. Lysosomal genes contribute to Parkinson’s disease near agriculture with high intensity pesticide use. NPJ Parkinson's Dis. (2024) 10, 87. https://doi.org/10.1038/s41531-024-00703-4
This milestone is transformative for the sugarcane industry. Scientists have already identified two key genes that help protect sugarcane from brown rust disease, a significant threat to farmers. Access to this genome data will accelerate breeding programs and increase the presence of desirable traits in sugarcane, ensuring its long-term sustainability as a vital crop. n
REFERENCE: Healey, A.L., et al., The complex polyploid genome architecture of sugarcane. Nature 628, 804–810 (2024). https://doi.org/10.1038/s41586-024-07231-4
The HudsonAlpha Genome Sequencing Center, led by faculty researchers Jane Grimwood, PhD and Jeremy Schmutz, contributed to this work.
9
SCIENCE FOR LIFE
NEW FINDINGS — MICRO GENOMICS
Big Data Look at a Tiny Creature Tardigrades are tiny animals often called water bears. They are known for their ability to survive in extreme environments, thriving in extremely hot temperatures, high pressures, and radiation levels more than 1,000 times what would be fatal to humans. How they survive in these inhospitable environments has long been a mystery. Previously, scientists discovered that tardigrades enter a dormant state during harsh conditions by expelling most of their body's water, drastically slowing metabolism, and forming a protective, glass-like cocoon of proteins around their cells. However, this adaptation alone does not fully account for their remarkable radiation resistance. In 2024, researchers gathered genomic, transcriptomic, and proteomic data from tardigrades before and after doses of radi- ation. From this rich data set, they discovered that some of the water bears in the study were a previously unidentified species. Scientists also found 2,801 genes with different expression lev- els after radiation exposure. Several of the upregulated genes were found to play a role in surviving high radiation.
One gene induces the production of betalains, a radiation-blocking pigment found in bacteria and some plants. Other genes appear to increase the speed and efficiency of DNA repair mechanisms by phase sepa- ration. Upon detecting DNA damage, specifically double-stranded breaks,
Unique Cell Division in Mouth Bacteria Most bacteria reproduce through binary fission, a process where a single cell divides into two identical daughter cells. However, a common oral bacterium uses a different mechanism. Corynebacteri- um matruchotii , often found along the gum line, are long filamentous cells capable of splitting into as many as 14 daughter cells simultaneously. This remarkable process, called simultaneous multiple fission, sets C. matruchotii apart. While other bacteria can divide into multiple cells at once, they typically do so only under unfavorable conditions, forming dormant spores that later activate when the environment improves. In contrast, C. matruchotii produces active cells immediately, making the first documented case of this reproductive strategy. Researchers discovered this unique proteins form a liquid-like hydrocarbon complex that stabilizes the broken DNA strands, recruiting repair proteins to facilitate efficient restoration. These genes are believed to result from horizontal gene transfer from bacteria, providing a fascinating glimpse into the evolutionary adaptations that enable tardigrades to withstand conditions that would be lethal to most other organisms. n REFERENCE: Li L, et. al., Multi-omics landscape and molecular basis of radiation tolerance in a tardigrade. Science . 2024 Oct 25;386(6720):eadl0799. Epub 2024 Oct 25. PMID: 39446960. https://doi.org/10.1126/science.adl0799
Invisible Ecosystem in Your Bathroom
You don’t need to travel to the tropics to witness extraordinary biodiversity; just take a step into your bathroom. New research from microbiolo- gists at Northwestern University has revealed a rich and diverse viral ecosystem thriving on
everyday bathroom items like showerheads and toothbrushes. By analyzing the surfaces of 34 toothbrushes and 92 showerheads, the study uncovered over 600 unique viral sequences, revealing a hidden microbial world flourishing in human-made environments. The vast majority of these viruses are bacteriophages, which target bacteria rather than humans and play a significant role in shap- ing microbial communities. Notably, 532 of the sequences correspond to bacteriophages known to infect 32 bacterial families. The discovery of additional sequences that don't match any known organisms under- scores the need for further exploration of these microbial ecosystems. This study offers new insights into the dynamic and intricate world of microbes that inhabit our daily spaces. Interestingly, data suggest minimal interaction between the microbial communities of toothbrush- es and showerheads, even within the same bathroom. More research is necessary to develop larger datasets on the microbial composition of various human-made environments. Understanding how these ecosystems evolve over time and in different conditions will help scientists understand the role of viral biodiversity in maintaining the delicate balance of beneficial and harmful bacteria in our homes. This research marks a significant step toward leveraging genomic technol- ogies to explore the fascinating microscopic world that lives on and around us every day and its implications for both environmental and human health. n
phenomenon using time-lapse imaging to study the formation of biofilms. Biofilms are complex communities of microorganisms that attach to surfaces, such as teeth, and play a crucial role in oral health. The ability of C. matruchotii to rapidly produce multiple daughter cells may explain how it can quickly recolonize the tooth surface after brushing. This discovery has significant implications for understanding bacterial growth and biofilm dynamics in the mouth. It also
raises intriguing questions: could other bacteria exhibit similar behaviors, and how might this influence strategies for targeting biofilms more effectively? This insight into C. matruchotii ’s reproduc- tive strategy could pave the way for new approaches to managing oral hygiene and combating biofilm-related challenges. n REFERENCE: S. Chimileski, et al., Tip extension and simultaneous multiple fission in a filamentous bacterium, Proc. Natl. Acad. Sci. U.S.A. 121 (37) e2408654121, https://doi.org/10.1073/pnas.2408654121
REFERENCE: Huttelmaier, S., et al., (2024). Phage communities in household-related biofilms correlate with bacterial hosts. Frontiers in Microbiomes , 3, 1396560. https://doi.org/10.3389/frmbi.2024.1396560
10
NEW FINDINGS — CANCER
Breast Cancer and Brain Metastasis Even though we’ve gotten better at treating breast cancer, there is still a concern that breast cancer cells can survive and spread to other parts of the body after treatment. Nearly half of
Battling T Cell Burnout T cells are a key part of the immune system and they help fight cancer by infiltrating tumors and attacking cancer cells. High levels of active T cells in and around tumors are linked to better survival rates and improved responses to immunotherapies. However, in the tumor
breast cancer patients who receive standard chemotherapies later develop cancer in other organs. Many treatments, like chemotherapy, have trouble reaching the brain because of a protective barrier, making the brain particularly vulnerable to metastasis. To better understand how breast cancer spreads to the brain, researchers studied small extracellular molecules released by cancer cells. These molecules, called microRNAs (miRNAs) regulate gene expression by binding to specific messenger RNAs (mRNAs) and preventing protein production. The team found that miR-199b-5p is uniquely secreted by breast cancer cells. This miRNA was found to be more abundant in breast cancer patients with brain metastases than those without, and was previously reported to be more prevalent in metastatic brain tumors than tumors originating in the brain. The brain has specialized cells called neurons and astrocytes that work together for proper brain functioning. Astrocytes convert the amino acid glutamate into glutamine and secrete lactate to fuel neurons. However, miR-199b-5p disrupts this metabolic pathway, increasing extracellular glutamate and lactate levels. These excess compounds are harmful to brain cells and actually provide fuel for the cancer cells to grow and spread. Researchers discovered that reversing miR-199b-5p's effects restored normal metabolic activity and reduced metastasis This suggests that targeting this pathway could be a promising therapeutic strategy for preventing brain me- tastasis among patients with breast cancer. n REFERENCE: Ruan, X., et al. Breast cancer cell-secreted miR-199b-5p hijacks neuromet- abolic coupling to promote brain metastasis. Nature Communications (2024) 15, 4549. https://doi.org/10.1038/s41467-024-48740-0
environment, T cells face constant stimulation and limited energy resources, leading to decreased func- tion or cell death. A recent study identified the protein METRNL as a key factor in this process. Previously
known for its role in glucose metabolism and heat generation during exercise or cold exposure, METRNL was found to play a critical role in T cell dysregulation. The study showed that overstimulated T cells release excessive METRNL, which in turn reduces the ability of the cell’s mitochondria to produce energy. Without sufficient energy, T cells lose function and die. In lab experiments, most T cells initiated the cell death process within 48 hours of being exposed to METRNL. Importantly, researchers discovered that removing METRNL in cancer cell models slowed tumor growth significantly. This finding suggests that targeting METRNL could enhance T cell activity and improve cancer treatment outcomes. Developing therapies to block METRNL, either alone or alongside immunotherapies, could be a promising approach to strengthen the immune response against cancer. n REFERENCE: Jackson, CM., et al. The cytokine Meterorin-like inhibits anti-tumor CD8+ T cell responses by disrupting mitochondrial function. Immunity. (2024) 57:8, 1864-1877. https://www.pubmed.ncbi.nlm.nih.gov/39111315 Smarter Cancer Treatments Genetic testing is becoming increasingly important in oncology and cancer treatment. DNA-based tests identify specific changes in the DNA sequence in tumor cells, while RNA-based tests reveal how the changes affect how genes work. This molecular-level view of cancer helps physicians choose the best treatments for each patient. However, tumors are made up of a mixture of different cells with unique genetic profiles. Currently, tumor genetic testing analyzes an average of all of these cells. Analyzing individual cancer cells is ideal for fully understanding a tumor but remains expensive and clinically inaccessible. The massive amounts of data generated from single-cell analysis also requires advanced bioinformatics tools to interpret and guide treatment decisions in a scalable way. Researchers at the National Institutes of Health recently devel- oped an artificial intelligence (AI) tool, PERCEPTION (PERsonalized single-Cell Expression-based Planning for Treatments IN ONcology), to predict patient responses to cancer drugs. The AI model was trained on bulk RNA sequencing data from many tumors and refined with single-cell data, targeting 44 FDA-approved cancer drugs.
PERCEPTION was validated using patient datasets for multiple myeloma and breast cancer, accurately predicting individual and overall patient responses to both single drugs and drug combina- tions. A key finding was that even if most cells respond to a drug, a few resistant cells can make the treatment ineffective, emphasizing the importance of targeting the most resistant cells. These findings pave the way for further development of this and other AI-developed tools to leverage genomic data and advance precision medicine. n REFERENCE: Sinha, S., et al. PERCEPTION predicts patient response and resistance to treatment using single-cell transcriptomics of their tumors. Nat Cancer (2024) 5, 938–952. https://doi.org/10.1038/s43018-024-00756-7
11
SCIENCE FOR LIFE
NEW FINDINGS — NEUROSCIENCE
How Hidden DNA Switches Might Protect Your Brain Scientists are cracking the code on a major brain mystery: why a protein called tau goes rogue and clumps together in diseases like Alzheimer’s and Parkinson’s. Normally, tau helps keep brain cells stable, but when it builds up too much, it can destroy them. Scientists wanted to understand how the gene encoding tau ( MAPT ) is controlled and if certain parts of the DNA near the gene could play a role in brain diseases. The researchers used advanced tools to study brain cells in the lab and post-mortem brain tissue. They looked for “cis-regulatory elements” (CREs), which are special DNA regions that help control gene activity by telling the brain when to make more tau. By mapping how DNA folds and connects, they found several CREs that were far away from the MAPT gene but still physically interact to turn it on or off. The team tested these CREs to see if they could activate MAPT and found that some regions were essential for tau production. They also looked at DNA from people with and without neurodegenerative diseases. They discovered that rare genetic changes in these CREs may actually protect against diseases by lowering tau production. This study highlights the importance of CREs in con- trolling tau levels in the brain. Understanding these regions better has the potential to help scientists develop new therapies for Alzheimer’s and related diseases by reducing tau production and its harmful effects. n REFERENCE: Rogers, B.B., et al. Neuronal MAPT expression is mediated by long-range interactions with cis-regulatory elements. American Journal of Human Genetics [2024] 111(2):259-279. https://doi.org/10.1016/j.ajhg.2023.12.015
Mitochondria Spit DNA into Brain Cells In addition to the large amounts of DNA found inside our cells’ nucleus, a smaller, circular strand of DNA is present within our cells’ mitochondria. This mitochondrial DNA (mtDNA) is usually maintained separately from nuclear DNA, but the transfer of mitochondrial DNA into nuclear DNA has been documented. Nuclear mitochondrial DNA (NUMT) is a sequence of mtDNA that has been expelled and integrat- ed into the nuclear genome. During this process, mtDNA acts like a virus, cutting nuclear DNA and inserting itself as the cut is repaired. The human genome shows evidence of accumulating NUMTs over time, most of which occur in noncoding regions and are thought to have little functional impact. This phenomenon was previously considered rare and mostly inconsequential. However, a 2024 study revealed that NUMTs occur more frequently in the human brain than in other body tissues. Even within the brain, certain regions had more NUMTs, suggesting that these transfers occur spontaneously during brain development or throughout life. These NUMTs may impact brain aging and lifespan, as researchers found that individuals with more NUMTs in their prefrontal cortex tended to die earlier than those with fewer. NUMTs are also frequently found in cancer cells, where they may contribute to genetic instability. Their accumulation in the brain could similarly disrupt genomic integrity and affect neural function. This connection emphasizes the need to further explore how NUMTs influence cellular aging and their role in neurodegenerative diseases. Scientists used cultured human skin cells to measure the rate of new mitochondrial DNA transfers. They found that new mito- chondrial DNA transfers into the genome occurred every 3–14 days. However, when cells were exposed to mitochondrial stress, NUMTs accumulated 4–5 times faster, indicating a connection between mitochondrial health and genomic stability. This ongoing transfer of mtDNA into the nuclear genome over our lifetime adds to the grow- ing understanding of mito-nuclear communication mechanisms that help shape human health. n REFERENCE: Zhou, W. et al. Somatic nuclear mitochondrial DNA insertions are prevalent in the human brain and accumulate over time in fibroblasts. PLoS Biology [2024] 22(8):e3002723. https://doi.org/10.1371/journal.pbio.3002723 placebo. The treatment also lowered the risk of progressing to more advanced stages by up to 39%. On average, amyloid plaques were reduced by 84% after 18 months of treatment, with the most signifi- cant benefits observed in individuals in the early stages of the disease. By directly targeting amyloid plaques, Kisunla offers a more focused approach to slowing disease progression and improving patients' quality of life. However, the cost of treatment is a critical factor. The financial burden on patients and healthcare systems is consider- able with a list price of approximately $696 per vial, or around $32,000 annually. Traditionally, Alzheimer’s treatments have only been able to focus on symptom management. Kisunla, along with other emerging therapies, represents a shift toward addressing the underlying causes of the disease, offering new hope for those affected. n
The laboratory of HudsonAlpha faculty researcher Nick Cochran, PhD, contributed to this work.
Plaque Busting Alzheimer’s Treatment
Alzheimer's disease is a progressive brain disorder that gradually impairs a person’s ability to think, remember, and perform daily tasks. It is the seventh leading cause of death in the United States. Alzhei- mer’s disease is characterized by the accumulation of amyloid protein plaques between neurons and tau protein tangles within neurons. In July 2024, the FDA approved the drug Kisunla ™ for treating early-stage Alzheimer's disease. Kisunla is an antibody-based therapy that binds to amyloid beta plaques, helping the immune system clear them from the brain. Administered through a monthly intravenous infusion, treatment continues until the plaques are removed. Clinical trials showed that patients receiving Kisunla experienced up to a 35% reduction in cognitive and functional decline compared to those on a
REFERENCE: U.S. Food and Drug Administration. FDA approves treatment for adults with Alzheimer’s disease. [2024] https://www.fda.gov/drugs/news-events-human- drugs/fda-approves-treatment-adults-alzheimers-disease
12
Page 1 Page 2 Page 3 Page 4 Page 5 Page 6 Page 7 Page 8 Page 9 Page 10 Page 11 Page 12 Page 13 Page 14 Page 15 Page 16 Page 17 Page 18 Page 19 Page 20 Page 21 Page 22 Page 23 Page 24 Page 25 Page 26 Page 27 Page 28 Page 29 Page 30 Page 31 Page 32Made with FlippingBook - Online magazine maker