Daily Archives: May 25, 2022

Bees are, in many ways, the darlings of the insect world. Not only do they play a crucial role in thriving ecosystems, but theyre also harbingers of the worsening consequences of climate change.

To bolster our knowledge of bee biology and behavior, a new effort dubbed the Beenome100 Project is building a first-of-its-kind library of dozens of different bee genomes. Researchers can use that information to tackle big picture questions like how to protect these tiny creatures, and how theyve evolved alongside us over time.

Beenome is just one of the many initiatives affiliated with the Earth BioGenome Project (EBP), an ambitious international effort to sequence the genomes of nearly 2 million named eukaryotic species. Eukaryotes have cells that contain nuclei and other organelles, setting them apart from other life forms like bacteria. This domain covers all plants, fungi, and animals, including bees.

READ MORE: World isnt meeting biodiversity goals, U.N. report finds

First launched in 2018, EBP aims to sequence the genomes of those species over the course of 10 years, housing them in a public database so that all researchers can have unfettered access to this extensive, unprecedented data. The sweeping project is largely made possible thanks to advancements in the field of genomic sequencing technology, which has made this work faster, cheaper and more accessible in recent years.

Bees face myriad threats in a warming world, including population decline, a loss of synchronicity with the flowers they pollinate and increased susceptibility to disease. In general, insects are vulnerable to climate change because being coldblooded makes them uniquely sensitive to temperature fluctuations, said Michael Branstetter, a research entomologist at the United States Department of Agriculture.

The extinction rate of insect species is eight times faster compared to mammals, birds and reptiles, according to the United Nations Environment Program, and if the total mass of insects continues to drop at its current annual rate, these creatures could vanish within a century. Bees are no exception to our own peril. Around a third of the crops we eat rely on animal pollinators, according to the USDA. Without bees, birds and other creatures, our pantries and refrigerators would look dramatically different.

If you picked any insect group to disappear, you wouldnt want to start with bees, because we would feel the effects for sure, Branstetter said.

The United States is home to approximately 4,000 native bee species, and the aim of Beenome is to help researchers answer such questions as the genetic underpinnings that make different species susceptible to climate change. The project has a goal of unlocking the blueprint for at least 100 species, and eventually sequencing more over time, said Jay Evans, a research entomologist at the USDA and co-lead of the project.

The broader Earth BioGenome Project will help map a massive branch on the tree of life, with many potential uses, like significantly improving our understanding of evolution and ecology. It will also inform research in fields like agriculture, medicine, biotechnology and more. But the reality of climate change is putting researchers feet to the fire.

Around 1 million animal and plant species face extinction, several potentially within the next few decades, due to forces like habitat loss and rising global temperatures, the United Nations estimates. That means Earth could lose up to 50 percent of its total biodiversity by 2100 without human intervention, according to the University of California, Davis.

For pollinator species, shifting temperatures and weather patterns shift also affect the natural timetables long adhered to by flowering plants a serious disadvantage to both the plant and the insects.

There are many reasons why genomes are useful tools for scientific research, Branstetter said, including assessing the genetic diversity of a species and identifying potential genomic signatures of sociality that underpin some species hive mentality. But the very real threat of losing entire species to environmental changes is also a consideration.

Should a species go extinct, its at least nice to know that weve documented the genome of that species, Branstetter added.

When it comes to pollination, some bees are generalists who will pollinate pretty much any flower they come across. Others specialize in specific botanical families or even species, and have evolved over time in ways that optimize their ability to retrieve pollen from their preferred plants.

One example of this is South Africas Rediviva bee, which specializes in the collection of oils from snapdragons. The relationship is an example of a bee adapting over time to be an ideal match for the flowers they frequent.

The spurs on the flowers that the bees stick their legs into vary in length, and theyve sort of co-evolved with the bees, Branstetter said. So the bees front legs also vary in length. That matched variation allows for greater efficiency of the pollinating process, a benefit to both the bees and the snapdragons.

Anna Childers co-leads the USDAs Ag100Pest Initiative sequencing arthropods like ticks, flies and weevils. She noted that its crucial to understand how bees, as sentinel insects of climate change, may be responding to fluctuating temperatures and seasons in order for us to protect potentially endangered species.

We kind of need to know how climate change might affect them, and having their genome is one way of learning this, she said.

So how does genetic code, gibberish to the untrained eye, help answer major questions?

Childers knows that peoples eyes tend to glaze over once you get into the alphabet soup (adenine, guanine, thymine and cytosine or A, G, T and C) that comprises genomes. Thats why she likes to use the metaphor of a map.

Genomes are like the most bare-boned map, where the basic geographic features are laid out but not much else. With a little more information, Childers said, you can start to add details like the locations of homes and businesses, or the traffic patterns of the busiest neighborhoods that differ depending on the time of day.

By bringing it all together in one place and having that map on which to place [other information,] it allows us to have a much more intricate understanding of whats happening, Childers said.

So far, members of 40 species are on their way to having their genomes sequenced. These bees were picked out of their natural environments, then frozen and sent to Hawaii-based labs tasked with extracting their DNA. It may sound counterintuitive to sacrifice the bees scientists aim to preserve, but dont worry they dont take enough individuals to harm the species as a whole.

Sample collection can be tricky first researchers have to actually find a member of the bee species theyre seeking to sample in the wild. For larger bees, a single part of their body like the thorax is usually enough to get a whole genome. But the tinier the bee, the more you need to retrieve genetic code.

WATCH: As bee populations decline, can technology help fill the gap?

For the small bees, theres only enough DNA if you do the whole bee. We just grind up wings, everything all together, Evans said.

Sometimes researchers can also take multiple bees from the same colony or location and pool them together to generate a genome, Branstetter noted.

Once DNA is extracted from Beenome bees in Hawaii, researchers there or in Mississippi (both locations have the technology) feed it to a sequencing machine in smaller portions.

You break that DNA down a little bit to maybe 20,000 base pair chunks. Then you put tags on the ends of each of those chunks, and then those are what go into this sequencing machine, Evans said.

After that, those sequenced chunks get stitched together in a process called assembly. The annotation phase comes next. Thats when a combination of researchers and automated analyses interpret stretches of genetic code to figure out which genes they correspond to.

The process, which concerns about a tenth of the total genome, cross references the genomes of other species to identify the genes that are shared across different forms of life. Other parts of the genome are assessed as well, including non-coding RNA and sites that regulate how genes are turned on.

The process of annotating is akin to noting those traffic patterns or key landmarks on a map. Once its complete, the seemingly endless series of four letters is transformed into a key that connects an organisms DNA to what researchers can observe about how a living member of the species goes about its daily life.

Bees captivate researchers for almost as many reasons as there are kinds of bees. For one, their behavior varies wildly across species. Some are social like the famously hive-minded honeybees and bumblebees but the majority lead solitary lives. Theres even variation within the same species in terms of living a social or solo life depending on external factors, noted Branstetter, who is involved with Beenome.

In the U.S., the Mojave poppy bee is native to a small, arid range across parts of Utah, Nevada and California. This tiny, solitary bee which belongs to a family that had not been sequenced previously specializes in pollinating local poppies that really only grow in certain conditions, and bloom for a short period during the spring.

Perdita meconis, otherwise known as the Mojave poppy bee, is pictured beside a dime to indicate its small size. Photo by Chelsey Ritner/USDA-ARS.

Their symbiosis is a prime example of how specialized the relationship between certain bees and plants can become, and just how crucial their mutual survival is. Both the bee and one of the flowers it frequents are under consideration for the endangered species list and face the threats of urbanization in their native habitat.

When Branstetters team sent the bees genome for sequencing, he said the result was one of the best genomes of a solitary bee generated thus far. He noted that the species unique biology and habitat checks a lot of boxes when it comes to the study of bees and their conservation.

Its a really tiny bee, so it was sort of challenging methodologically to see, Can we get a good genome from it?' he said. And its from the desert Southwest, so it covers a geographic region and a habitat that we dont have many representatives of for bees.

The researchers intend to collect more Mojave poppy bees in order to improve their understanding of the populations genetic diversity, but last year they didnt find a single specimen, illustrating just how tricky that field work can be. Branstetter hopes thats an example of bet hedging, when bees skip a season of poor, dry weather conditions so that they can reappear the following year.

Bee genomes can also help us map humans shared history with the rest of the natural world. Margarita Lpez-Uribe, an associate professor of entomology at Penn State University, worked with her team to sequence the squash bee genome, a species that specializes in the pollination of members of the cucurbita genus, including squash and pumpkins.

Although squash bees can be found across the U.S. today, they were originally native to southwestern parts of the country, plus modern-day Mexico. They happily feasted on wild cucurbita plants that Indigenous populations in those regions began domesticating 10,000 years ago. But as people migrated away from that region and the scale of agriculture increased over the course of millennia, they brought their cultivated cucurbits with them, and the squash bees followed suit.

This bee had been moving with the cultivation of crops and the movement of humans throughout North America, Lpez-Uribe said.

Squash bees are pictured collecting nectar inside a squash blossom. Photo courtesy Laura Jones.

By using a combination of different genomic information, she and her team estimated when geographically separated squash bees split off from each other. The squash bees that now live in the Northeast are genetically highly divergent, Lpez-Uribe said, compared to the ancestral populations that still live in the southwest and Mexico. That means that squash bees have gone through major adaptive processes in their journey across land and time.

Its clear that genomes can help us solve mysteries of evolution and ecology. But we can also call on them to help solve some of the most pressing crises facing humanity. Childers pointed to a beetle whose genomic sequence allowed researchers to understand how its able to break down wood. That kind of information, she noted, could help us identify more efficient ways to do the same thing in order to develop alternate fuels, or clean up environmental damage caused by catastrophes like oil spills.

Its hard to know what species were going to pluck out of the environment that lead us to the innovations that will transform the future, Childers said. Having a bank of genomes at our fingertips is key to unlocking that wealth.

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What genetic sequencing can reveal about the secret lives of bees - PBS NewsHour

Will invest $250,000 in companies advancing genome engineering technology and science

PRINCETON, N.J., May 24, 2022 /PRNewswire/ -- The venture capital firm SOSV and its startup development program IndieBio, have teamed up with the Genome Project-write (GP-write), a global nonprofit genome engineering consortium, to launch the GP-write Startup Team, a project designed to vet, select, fund, and advise new ventures advancing the technology and science of writing genomes. The aim of the partnership is to improve access to R&D resources for viable startups in this space and increase visibility to their important work.

SOSV'S INDIEBIO AND GENOME PROJECT-WRITE PARTNER TO FUND AND ADVISE STARTUPSWill invest $250,000 to winning applicants

The partnership will provide GP-write companies with the unique opportunity for funding and advising from the GP-write Startup Team of world leaders. Selected companies will be invited to participate in the next IndieBio cohort to receive programming, network access, mentorship, and guidance from industrial experts, biotech founders, and patent licensing experts so the startups can quickly advance toward a next round of financing.

Investing in revolutionary technology that promises the betterment of humanity and the planet, SOSV has $1.2 billion in assets under management. From SOSV, IndieBio's pre-seed life-science startups receive a $275,000 investment (up to $500,000 or more with follow-on support) and join a four-month program that provides on-site expertise, access to modern laboratories, and an unparalleled mentor network. IndieBio's San Francisco and New York programs each run two, 15-company cohorts each per year. The first round of GP-write startup companies will join the IndieBio September 2022 cohort.

"SOSV's IndieBio and GP-write have a shared visionto expedite advances in large-scale genome editing and synthesisand believe the evolution of these technologies will lead to transformational change in personalized therapeutics," said IndieBio General Partner Stephen Chambers. "Our goal is to support developments in personalized gene and cellular therapies to drive dramatic cost reductions, create solutions for reversing climate change, and produce an entirely new class of engineered materials."

"The GP-write Startup Team includes world leaders across academia and industry with a track record of successful entrepreneurship in synthetic biology.We are thrilled to be uniting in this effort, which pairs GP-write's mission with the SOSV-IndieBio expertise in startup innovation," said Amy Cayne Schwartz, President and General Counsel of GP-write. "Translating valuable innovation from academia to the marketplace for the benefit of society at large is the impetus for this Startup Partnership."

Specifically, the Request For Proposals (RFP) is seeking to fund innovative, early stage startups advancing the science and technology of genome engineering. Some high priority areas include: Software Tools for Gene/Genome-Scale Design, Improvements in DNA Synthesis, Genome Editing (e.g. expand multiplexity and precision of DNA editing), or Chromosome and Organism Engineering. To learn more or submit a proposal before July 1, 2022, email amy@engineeringbiologycenter.org.

About SOSV

SOSV is a global venture capital firm headquartered in Princeton, NJ. The firm has more $1.2 billion in assets under management and specializes in the early stage development of deep tech companies focused on human and planetary health. SOSV operates the startup development programs HAX(hard tech), IndieBio(life sciences), Chinacceleratorand MOX (cross-border growth), and dlab(blockchain). To learn more, go tohttps://sosv.com/.

About IndieBio

SOSV's IndieBio is the leading life sciences startup program. With locations in New York City and San Francisco, IndieBio's mission is to turn scientists into entrepreneurs who can save lives and save the planet. IndieBio is devoted to building early stage startups that are solving humanity's most pressing problems with climate technology, synthetic biology, alternative foods, health tech, and much more. To learn more, go to https://indiebio.co/.

About Genome Project-write

GP-write, conceived as a sequel to The Human Genome Project, leverages advances in high throughput genome sequencing, gene editing and synthetic biology to drive dramatic cost reductions and expedite whole-genome writing and redesign. Supporting work of multi-institutional and interdisciplinary research teams engaged in broad public outreach, the organization includes nearly 300 scientists, affiliated with more than 100 institutions/companies in 17 countries. GP-write's Foundry and Startup Ecosystem is led by the GPW Industrial Advisory Board comprised of world leaders in genome editing and synthesis technologies.To learn more, follow GP-write: http://www.engineeringbiologycenter.org.

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SOSV'S INDIEBIO AND GENOME PROJECT-WRITE PARTNER TO FUND AND ADVISE STARTUPS - Kilgore News Herald

Complete mitochondrial genome assembly

The mitogenomes of St, Sc, and StSc were assembled into five to two subgenomes through de novo assembly using 5.3 to 6.6Gb PE reads. Each assembly was validated by conducting PCR analysis and sequencing (Tables S1 and S2, Fig. S1). The St mitogenome size was 756,058bp, and it was composed of five circular subgenomes of lengths 49,230 to 297,014bp. The total number of non-redundant genes was 78, consisting of 37 PCGs, 19 ORFs, 3 rRNAs, and 19 tRNAs (Table 1, Fig. S2A). The Sc mitogenome was 552,103bp in size with two subgenomes (338,427 and 213,676bp). The total number of non-redundant genes was 77, consisting of 37 PCGs, 20 ORFs, 3 rRNAs, and 17 tRNAs (Table 1, Fig. S2B). The StSc mitogenomes were 447,645bp in size with a major circular DNA of 398,439bp and a minor subgenome of 49,206bp. The total number of non-redundant genes was 77, consisting of 37 PCGs, 20 ORFs, 3 rRNAs, and 17 tRNAs (Table 1, Fig. S2C).

A total of 71 genes were shared among the three mitogenomes. Some genes were unique in each mitogenome: four ORFs (orf131, orf 190, orf 240, and orf 279), and three tRNAs (trnI-GAU, trnL-CAA, and trnV-GAC) were unique in the St mitogenome; five ORFs (orf109d, orf111, orf140, orf185, orf240) and one tRNA (trnfM-CAT) were unique in the Sc genome; and five ORFs (orf111, orf127, orf131, orf140, orf185) and one tRNA (trnV-GAC) were unique in the StSc mitogenome (Table 2).

Mitochondrial plastid DNA (MTPT) has been reported in various plants, such as Amborella trichopoda, Zea mays (maize), and Cynanchum wilfordii34,35,36. The degree of MTPT was examined by sequence comparison with the S. tuberosum plastome sequence (GenBank accession No. no. KM489056)37. Consequently, the St, Sc, and StSc mitogenomes were approximately 1.08.0%, 2.98.0%, and 3.14.0% considered as MTPT, respectively. Overall, approximately 1.08.0% were identified as MTPT (Table 1, Fig. S2).

Further, nuclear mitochondrial DNA (NUMT) has also been reported in various plants, such as Arabidopsis thaliana and Cucumis sativus (cucumber)38,39. NUMT was identified by sequence comparison with the S. tuberosum nuclear genome sequence (SolTub_3.0, https://www.ncbi.nlm.nih.gov/assembly/GCF_000226075.1/). Consequently, the St, Sc, and StSc mitogenomes were approximately 17.257.7%, 16.117.4%, and 10.116.3%, respectively, which were considered to be derived from or transferred to nuclear genomes accordingly. Overall, approximately 10.757.7% was identified as NUMTs. A total of 57.7% was identified in St subgenome 4, which has a very small genome size (Table 1, Fig. S2).

Homologous recombination (HR) can be mediated by repeat sequences in St, Sc, and StSc mitogenomes. The St, Sc, and StSc mitogenomes accounted for approximately 2.219.4%, 4.821.3%, and 5.725.9% of repeat sequences in which the repeat ratio was also positively correlated with the subgenome size (Table 1, Figs.1 and S2). The five St subgenomes exhibited diverse numbers of dispersed repeats: 300 (mitogenome coverage: 19.4%), 211 (15.2%), 41 (5.5%), 18 (2.2%), and 39 (4.9%) in each subgenome (Tables 1 and S5, Figs.1A and S2A). The two Sc subgenomes included 460 (25.9%) and 198 dispersed repeats (15.2%) (Tables 1 and S5, Figs.1B and S2B). Further, the two StSc subgenomes contained 480 (21.3%) and 39 (4.8%) dispersed repeats (Tables 1 and S5, Fig.1C and S2C). In contrast, tandem repeats were selected with adjacent sequences of at least two copies and up to 50bp. The St, Sc, and StSc mitogenomes had only 17, 20, and 16 tandem repeats, respectively (Table S6).

Chord diagram of three Solanum mitogenomes. (AC) represent the homologous regions of the subgenomes. R1 to R3 represent the large repeats that might cause homologous recombination among the corresponding subgenomes. St: S. tuberosum accession no. PT56, Sc: S. commersonii accession no. Lz3.2, StSc: somatic hybrid accession no. HA06-9.

Two large repeats (more than 1kb) were identified in the St subgenome 1. R1 was 11,916bp, and R2 was 7500bp. In contrast, St subgenome 2 had only R1, and subgenome 3 had only 1589bp of R3. Similarly, the R1 sequence co-existed in St subgenomes 1 and 2. The R2 repeat is shared between subgenomes 1 and 4 (Table S5, Figs.1 and S2), which might contribute to the HR between different subgenomes. The Sc mitogenomes had two multipartite structures, in which three large repeats of more than 1kb were identified (R1: 16,857bp, R2: 10,094bp, and R3: 1024bp), which might contribute to recombination events between subgenomes (Table S5, Figs.1 and S2). The StSc mitogenomes contain four large repeats (more than 1kb) (R1, 11,916bp; R2, 11,846bp; R3, 1643bp; and R4, 1024bp) that might contribute to subgenome reshuffling (Table S5, Figs.1 and S2).

We compared plastomes, mitogenomes, and nrDNAs among St, Sc, and StSc genomes. The StSc plastome was identical to Sc plastome37. Meanwhile, the StSc mitogenome shows a complicated structure with unique genes derived from both species (Table S3, Fig.2). Among 71 common genes, 21 PCGs (nad3, nad4, nad4L, nad5, nad6, sdh3, cox2, cox3, atp1, atp4, atp8, atp9, ccmB, rps3, rps4, rps12, rps13, rpl5, rpl10, rpl16, and mttB) were found identical across the three mitogenomes (denoted as green boxes on Fig.2) and their origin in the StSc genome could not be determined; 12 PCGs (nad1, nad2, nad7, nad9, sdh4, cob, cox1, ccmC, ccmFc, rps10, rpl2, and matR) were found identical with Sc (represented as sky-blue boxes in Fig.2) and 2 PCGs (atp6 and ccmFN) were identical with St (pink boxes in Fig.2). Therefore, it is likely that the majority of the somatic hybrid mitogenomes originated from Sc (Fig.2).

The origin of mitogenome recombination block in somatic hybrid (StSc) (A) Subgenome 1 of somatic hybrid mitogenome (B) Subgenome 2 of somatic hybrid mitogenome. The pink and sky-blue triangles on the black middle line indicate genes derived from S. tuberosum and S. commersonii, respectively. The green diamond boxes indicate genes of unknown origin.

GISH data using Sc genome probes revealed strong signals in 24 chromosomes but weak signals in the other 24 chromosomes in the StSc somatic hybrid (Fig.3A). We also assembled and compared 45S nrDNA cistron sequence of three species. For example, multiple aligned position at 191bp represents T genotype in St and C genotype in Sc. However, in StSc, it was identified that 75.6% of T and 24.4% of C were present. In conclusion, the overall 45S nrDNA sequences of StSc revealed both genotypes with average about 70 and 30 ratio for Sc and St, respectively (Fig.3B).

Detection of nuclear genome fusion in somatic hybrid. (A) GISH analysis of somatic hybrid (HA06-1 clone) using S. tuberosum specific-probes. The red signal of 24 arrows indicates the S. commersonii nuclear subgenomic distribution. (B) Schematic diagram of 45S ribosomal DNA cistron of Solanum species. StSc summary represents the percentage of St or Sc genotypes in the 45SnrDNA sequence.

In summary, St, a dihaploid of tetraploid cultivated potato, has five mitogenomes. Sc, a diploid wild potato, has two mitogenomes. Somatic hybrids developed via protoplast fusion of these two diploids contain the Sc-unique plastome37 but recombined mitogenomes and nuclear genomes derived from both St and Sc genomes (Fig.4).

Schematic diagram of mitogenome in parental species and their somatic hybrids. (A) S. tuberosum (St), (B) S. commersonii (Sc), and (C) somatic hybrid (StSc). S. tuberosum and S. commersonii have five and two subgenomes, respectively, which are fused into two subgenomes in the somatic hybrid generated by protoplast fusion. The origin of chloroplast genome in somatic hybrid has been determined based on sequence comparison among chloroplast genome sequences of parental species and that of the somatic hybrid.

A total of 35 PCGs were common across Solanaceae. The nonsynonymous substitution (Ka), synonymous substitution (Ks), and their ratios were calculated. The Ka values ranged from 0 to 0.119 with a 0.003 of median value. The nad4 and nad4L genes had the lowest Ka values, while atp6 had the highest Ka value. The Ks values ranged from 0.02 to 0.228 with a 0.01 of median value. Moreover, mttB and atp6 had the lowest and highest Ks values, respectively. Lastly, the Ka/Ks values ranged from 0 to 3.528 with a median value of 0.286 (Table S8, Fig.5A). A Ka/Ks value of more than 2 was observed due to the extremely low Ks value.

Mitochondrial gene diversity in Solanaceae family. (A) non-synonymous substitution (Ka) and synonymous substitution (Ks) values among the 12 Solanaceae species. Ka and Ks values were calculated with 35 protein-coding genes by CodeML program. (B) Variations of atp6 are shown by the phylogenetic tree and multiple comparisons of amino acid sequences. The conserved domain has been determined through NCBI BLASTP search.

Although the Ka and Ks values were generally low, ccmFc and mttB exhibited high Ka/Ks values of more than 1, indicating that these genes were positively selected during evolution (Fig.5A). Considering that atp6 showed a high mutation rate above 0.1. Ka and Ks values relative to the other genes, the amino-acid sequences corresponding to atp6 were compared among Solanaceae species, which revealed that amino acid sequences were variable at the N-terminus but conserved at the C-terminus (Fig.5B).

Phylogenetic trees were constructed using various programs, including RAxML, MEGA7, PhyML, and BEAST to examine the topology of the species. Trees treated with RAxML, PhyML, and BEAST displayed the same topology, while those treated with MEGA7 exhibited slightly different topologies (Fig. S3). In trees generated using RAxML representing an optimized topology (Figs.6 and S3), Solanaceae species were divided into two subfamilies, Solanoideae and Nicotianoideae, and the somatic hybrid exhibited a moderate branch between St and Sc. During the evolution of Solanaceae mitogenome, first, rps1 and rps19 were present in Solanaceae, however, these were omitted completely in Oleaceae. Next, rps7 was confirmed to be completely deleted in Solanaceae compared to Oleaceae. Lastly, ycf14 in all Nicotianoideae species was pseudogenized in the divergence period between Solanoideae and Nicotianoideae (Fig.6).

Phylogenetic relationship of 13 Solanaceae species using 35 protein-coding gene sequences commonly conserved in mitogenomes. The maximum likelihood tree was constructed using RAxML program with GTR++I model (based on jModelTest2) and a bootstrapping value of 1000. The bootstrap value (>=0.5) is shown on the node. Deleted genes and pseudogenes specifically within each group in the tree have been also shown by red and black boxes, respectively. Olea europaea in the Oleaceae family has been used as an out-group.

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Lead development candidate SG-5-00455 shows potential to become first in class PAI-1/2 inhibitor that directly targets mucosal healing in patients with inflammatory bowel disease (IBD)

BRISBANE, Calif., May 24, 2022 /PRNewswire/ -- Second Genome, a biotechnology company that leverages its proprietary platform to discover and develop precision therapies and biomarkers, presented data demonstrating the Company'sdevelopment candidate, SG-5-00455, improves epithelial barrier function and promotes mucosal healing by effectively inhibiting plasminogen activator inhibitor (PAI)-1/2 activity in the intestines. The data were presented at Digestive Disease Week 2022 Annual Meeting, held May 21-24 virtually and in San Diego, California.

Second Genome Logo (PRNewsfoto/Second Genome)

There is a strong correlation between the upregulation of SERPINE1 (PAI-1) and chronic inflammation in IBD. Local delivery of SG-5-00455 to the gastrointestinal mucosa of diseased mice demonstrated efficacy by inhibiting PAI-1 activity, which in excessive amounts adversely impacts wound healing, immune cell modulation and tissue remodeling. By selectively targeting the PAI-1 pathway at the mucosa, SG-5-00455 improves epithelial barrier function by regulating extracellular matrix production and reducing profibrotic inflammation. SG-5-00455 demonstrates the potential to directly target mucosal healing, a key therapeutic goal in the treatment of IBD," said Joseph Dal Proto, Ph.D. "SG-5-00455 has the potential to become a first-in-class treatment for patients with IBD in which mucosal healing is inadequately addressed by current standards of care."

This data was presented during a poster session at DDW 2022. The information is provided below:

Session Title: Non-Immune Cells in Intestinal Inflammation: Epithelium and StromaAbstract Number: 3698252Title: Identification and Development of a 1st in Class Naturally-Derived Protein that Drives Mucosal Healing and is Orally Delivered by an Engineered Cellular Therapy Targeting the Gastro-Intestinal Tract

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In addition to SG-5-00455, Second Genome has presented data on the identification of immunomodulatory peptides with therapeutic potential using their proprietary technology-enabled platform (abstract number: 3699744) which was presented during another poster session at DDW 2022.

SG-5-00455 is an orally delivered, engineered biotherapeutic modulator of the PAI1/2 pathway that is designed to work locally within the gastrointestinal tract to promote mucosal healing and improve barrier function in IBD patients. In vitro, SG-5-00455 demonstrated direct binding to PAI-1, functional inhibition of PAI-1/2 function and improvement in epithelial barrier function. In pre-clinical colitis models, oral administration of SG-5-00455 reduced pathology scores for inflammation and restored barrier function levels, as well as improved dysregulated tissue repair and fibrosis-associated gene expression and proteins levels. Mechanism of action studies revealed interaction with, and modulation of, fibrinolysis pathway members, which were found to be upregulated in IBD patient samples in multiple clinical cohorts. This will provide the basis for a potential biomarker to identify patients likely to respond to SG-5-00455. SG-5-00455 is currently in IND-enabling studies, and the Company anticipates filing an investigational new drug (IND) application with the U.S. FDA late 2022.

The SG-5-00455 poster (#3698252) entitled, "Identification and Development of a 1st in Class Naturally-Derived Protein that Drives Mucosal Healing and is Orally Delivered by an Engineered Cellular Therapy Targeting the Gastro-Intestinal Tract," and the poster on the identification of immunomodulatory peptides utilizing our proprietary technology-enabled drug discovery platform (#3699744) will be made available on the Company's website at https://www.secondgenome.com/events/.

About Second Genome

Second Genome is a biotechnology company that leverages its proprietary technology-enabled platform to discover and develop transformational precision therapies based on novel microbial genetic insights. We built a proprietary drug discovery platform with machine-learning analytics, customized protein engineering techniques, phage library screening, mass spec analysis and gene-editing that we couple with traditional drug development approaches to progress the development of precision therapies for wide-ranging diseases. Second Genome is advancing lead programs in IBD and cancer into IND-enabling studies. We also collaborate with industry, academic and governmental partners to leverage our platform and data science capabilities. We hold a strategic collaboration with Gilead Sciences, Inc., utilizing our proprietary platform and comprehensive data sets to identify novel biomarkers associated with clinical response to Gilead's investigational medicines. We also hold a strategic collaboration with Pfizer (formerly Arena Pharmaceuticals) to identify microbiome biomarkers associated with clinical response for their lead program in gastroenterology, etrasimod. For more information, please visit http://www.secondgenome.com.

Investor / Media Contact:650-440-4606partnering@secondgenome.com

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Second Genome Presents New Data at Digestive Disease Week (DDW) 2022 Demonstrating that SG-5-00455, a Potential First-in-Class Precision Therapeutic,...

New research led by a University of Florida scientist shows a development regulator can help plants grow. In the bigger picture, the studys results also may help genome editing and, as a result, plant breeding.

Development regulators are genes that regulate plant development and growth. UF/IFAS scientists have discovered that one such gene can help deliver DNA into a plant to promote shoot growth from either a stem of a whole plant or young leaves cultured in a petri dish.

The study shows that injecting a plant developmental regulator known as PLT5 into the stem helps some snapdragons and tomatoes grow into new shoots. In addition, scientists found that the PLT5 can help young leaves or petioles of cabbages grow into a whole plant after culturing them in the petri dish.

Generally, it is extremely difficult for cells from some plants to grow into whole plants from a tissue culture, said Alfred Huo, an assistant professor of horticultural sciences at the UF/IFAS Mid-Florida Research and Education Center. By applying PLT5, scientists can more effectively deliver genes or DNA fragments into plant cells, which means plants can grow from the cellular level to adulthood more efficiently.

This research can help scientists address some questions in basic plant breeding, including how to get certain genes into plants, Huo said. It can also help scientists as they apply genome editing to many plant species.

This finding can accelerate a breeding program, Huo said. You want to use genome editing for plant breeding. But you need to deliver a genome editing toolbox into plants to make the editing happen. With this process, scientists can eventually create some desirable traits in plants and develop new cultivars. In this case, the PLT5 regulator can help deliver this toolbox and help grow young leaves or stems into new plants carrying these desirable traits.

More than 20 scientists across Florida including Huo are part of the UF/IFAS Plant Breeding team. They develop new varieties of citrus, tomatoes, strawberries, blueberries, cattle forages, peanuts, sugarcane, ornamental plants, and more.

Source: ifas.ufl.edu

Link:
UF scientists may have found a way to more efficiently apply genome editing to plant breeding - hortidaily.com

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Genome-wide identification of carbapenem-resistant Gram-negative bacterial (CR-GNB) isolates retrieved from hospitalized patients in Bihar, India |...