How to make better biofuels? Convince yeast it's not starving

Phys.org | November 14, 2019

Yeast already helps make bread and beer and cranks out the biofuel ethanol, but scientists believe it can be used to create an even more efficient fuel called isobutanol. Normally, yeast only creates a tiny amount of isobutanol. Now researchers at Princeton University have discovered a genetic switch that significantly ramps up production. The findings, published Nov. 13 in the journal Cell Systems, showed that the researchers were able to increase isobutanol production by roughly five times over that of standard yeast strains by making the yeast much more tolerant to isobutanol's toxic effects. Isobutanol has about a 25% greater energy density than ethanol and is much better suited for use in vehicles than current ethanol-based fuels. Biofuels can be a renewable and environmentally friendly alternative to petroleum-based fuels.

Spotlight

You might have heard of CAR-T cell therapy as a “miracle cure” for cancer. The approval of Novartis’ Kymriah, the first CAR-T therapy, made headlines in August as it was the first gene-edited cell therapy for cancer to make it to the market. The approval of Gilead and Kite Pharma’s CAR-T therapy Yescarta followed this week, leading the way for many other versions that are expected to arrive on the market in coming years to treat different types of cancer, with better efficacy and safety, and lower prices.

Spotlight

You might have heard of CAR-T cell therapy as a “miracle cure” for cancer. The approval of Novartis’ Kymriah, the first CAR-T therapy, made headlines in August as it was the first gene-edited cell therapy for cancer to make it to the market. The approval of Gilead and Kite Pharma’s CAR-T therapy Yescarta followed this week, leading the way for many other versions that are expected to arrive on the market in coming years to treat different types of cancer, with better efficacy and safety, and lower prices.

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INDUSTRIAL IMPACT

Novo Holdings Leads US$21M Series A Financing in BIOMILQ

Novo Holdings | October 21, 2021

BIOMILQ is developing a novel infant feeding option, derived from human mammary cells, to better meet infants' nutritional needs and with a lower carbon footprint than traditional bovine-based infant formula. Earlier this year, BIOMILQ announced it had successfully produced a milk product with many of the same macronutrients that are known to be abundantly present in breastmilk in its lab based in Research Triangle Park in North Carolina, US. In the US, it is estimated that 75%1 of women are unable to exclusively breastfeed for the six months after birth as recommended by the American Academy of Pediatrics and the World Health Organization. Breastfeeding can be difficult due to latching issues, birth complications, discomfort or pain, exhaustion, inadequate milk supply, amongst other reasons. Alternative supplements, such as bovine-based infant formula, can lack the nutritional and bioactive composition found in breast milk. BIOMILQ's technology and solutions can be transformative in the field of infant nutrition, a market with a significant need for innovation. "Our mission is to make a growing and positive impact on health, science and society. We are delighted to support BIOMILQ through its journey pioneering mammary biotechnology. Its products have the potential to disrupt the infant supplemental feeding industry. We aim to use our scientific knowledge, operational expertise and global network to further strengthen the Company's ability to improve lives. Kartik Dharmadhikari, Partner at Novo Groand BIOMILQ Board Director Michelle Egger, Chief Executive Officer and Co Founder of BIOMILQ, added: "We are very pleased to have such experienced investors in our Series A financing. Novo Holdings, as a leading international life science investor, lends significant market experience and technical knowhow to BIOMILQ's mission to nourish healthier infants, empower parents through choice, and contribute to a healthier planet. The investor syndicate was led by Novo Holdings, with participation from Breakthrough Energy Ventures, Blue Horizon, Spero Ventures, Digitalis Ventures, Green Generation Fund and Gaingels. About Novo Holdings A/S Novo Holdings A/S is a private limited liability company wholly owned by the Novo Nordisk Foundation. It is the holding company of the Novo Group, comprising Novo Nordisk A/S and Novozymes A/S, and is responsible for managing the Novo Nordisk Foundation's assets. Novo Holdings is recognized as a leading international life science investor, with a focus on creating long-term value. As a life science investor, Novo Holdings provides seed and venture capital to development-stage companies and takes significant ownership positions in growth and well-established companies. Novo Holdings also manages a broad portfolio of diversified financial assets. Further information. About BIOMILQ BIOMILQ's mission is to close the nutritional gap between infant feeding options. In June 2021, BIOMILQ announced its capability of producing a milk product, derived from human mammary cells, that has macronutrient profiles that closely match the expected types and proportions of proteins, complex carbohydrates, fatty acids and other bioactive lipids that are known to be abundantly present in breastmilk. 1 "Breastfeeding Among U.S. Children Born 2011–2018, CDC National Immunization Survey." Centers for Disease Control

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CELL AND GENE THERAPY

PacBio Acquires Omniome, a DNA Sequencing Startup, for up to $800 Million

PacBio | July 26, 2021

Pacific Biosciences has had no trouble growing its business on its own in the year and a half since its acquisition by Illumina was blocked by the Federal Trade Commission due to concerns that the combination would establish a monopoly in DNA sequencing. Earlier this year, the sequencer manufacturer received a staggering $900 million investment from SoftBank—a commitment almost as large as the $1.2 billion promised by Illumina for the planned acquisition. PacBio is now making its acquisition, setting out a deal for up to $800 million to acquire Omniome, another provider of DNA sequencing technology. The majority of the transaction is comprised of planned upfront payments totaling about $600 million. This will be paid out in $300 million in cash and 9.4 million shares of PacBio common stock. The additional $200 million will come from milestone payments made when Omniome meets certain specified objectives, which will also be paid in a mix of cash and shares. PacBio has committed a small number of its current investors to a private issue of common stock to fund the acquisition. The total gross proceeds from this deal are expected to be about $300 million. Casdin Capital, SoftBank subsidiary SB Northstar LP, and T. Rowe Price Associates are among the investors who will buy approximately 11.2 million shares of PacBio stock for $26.75 per share, which is slightly less than the stock's closing price on the last full day of trading before the buyout was announced. PacBio will be able to extend the capabilities of its single-molecule, real-time sequencing technology, or SMRT Sequencing, for use by its clients in biomedical and infectious disease research, as well as therapeutic and diagnostic development, after the transaction is completed. PacBio's technology is based on long-read sequencing, which analyzes long strands of DNA at a time and can detect larger genomic variants and structural changes than short-read methods—though long-read sequencing has a higher potential error rate in those readings. Meanwhile, Omniome has created its short-read technology that concentrates on the proteins that bind to DNA to generate what it claims are more accurate analyses than existing short-read sequencers. Combining the two technologies is reminiscent of Illumina's planned acquisition of PacBio, which would have merged the latter's long-read technology with Illumina's short-read sequencing. The merger is a significant boost for Omniome, which has attracted several life sciences, investors since its inception in 2013. Each of its most two funding rounds—a series B in mid-2018 and a series C in early 2020—raised $60 million, bringing the San Diego-based startup's total funding to over $130 million.

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MEDICAL

Duke Researchers Identify Genetic Mechanism in Brain Lesion Formation Using Single-Cell DNA Sequencing from Mission Bio

Mission Bio | March 15, 2022

Mission Bio, the pioneer in high-throughput single-cell DNA and multi-omics analysis, announced new findings by Daniel Snellings from the lab of Douglas Marchuk, PhD, at Duke University School of Medicine using single-cell DNA sequencing to identify genetic mechanisms leading to the development of cerebral cavernous malformations (CCMs). The study, published today in the journal Nature Cardiovascular Research, is the latest demonstration of how Mission Bio's Tapestri Platform is allowing researchers to probe new aspects of biology at a single-cell resolution not possible with bulk sequencing. Dr. Marchuk is Professor of Molecular Genetics and Microbiology at Duke. CCMs, a blood vessel abnormality that can lead to brain hemorrhages, have long been associated with developmental venous anomalies (DVAs), a typically benign but irregular vascular arrangement often found near sporadic CCMs – though researchers had yet to prove a link. In the paper, Snellings and colleagues sequenced DNA from three CCM patient samples to see if somatic mutations in MAP3K3 or PIK3CA – common in patients with CCMs – co-existed in the same cells. Single-cell DNA sequencing with Tapestri found co-occurring mutations in the cells of all three samples, a pattern that could not be determined by bulk sequencing. Further, the group found that the CCMs and the associated DVAs harbored identical mutations in PIK3CA, but that mutations in MAP3K3 were only found in the CCMs. Because of the pattern of PIK3CA and MAP3K3 co-occurrence in CCMs, the team could assess the temporal pattern of genetic mutations associated with disease progression. They determined that DVA is the first lesion to occur, and that CCM development happens only after acquisition of an activating MAP3K3 mutation in a cell of the existing DVA.sazsz It was surprising to find that something as common as DVAs—which are present in up to 16% of people—could be caused by a cancer driver mutation. This explains why sporadic CCMs are often found in the vicinity of a DVA, and may explain why other diseases like pontine gliomas are also found near DVAs." Snellings. Tapestri is regularly deployed in cancer research to detect somatic mutations in clonal populations as a way of tracking tumor development, and the researchers adapted that methodology to evaluate the relationship between DVAs and CCMs. Since DVAs are not regularly biopsied, the researchers also confirmed the presence of circulating mRNAs in patients with both CCM and DVA related to this biological pathway, in plasma – a first step toward establishing a biomarker for CCM risk in patients with DVAs. We expect this research will have a meaningful impact for patients at risk for developing spontaneous cerebral cavernous malformations, which can lead to strokes or even death, This paper is a powerful new demonstration that there are many disease areas where single-cell DNA sequencing is helping elucidate the mechanisms of disease development, and identifying potential targets for diagnostics or therapeutics." Yan Zhang, PhD, CEO of Mission Bio. About Mission Bio Mission Bio is a life sciences company that accelerates discoveries and cures for a wide range of diseases by equipping researchers with the tools they need to better measure and predict our resistance and response to new therapies. Mission Bio's multi-omics approach improves time-to-market for new therapeutics, including innovative cell and gene therapies that provide new pathways to health. Founded in 2014, Mission Bio has secured investment from Novo Growth, Cota Capital, Agilent Technologies, Mayfield Fund, and others. The company's Tapestri platform gives researchers around the globe the power to interrogate every molecule in a cell together, providing a comprehensive understanding of activity from a single sample. Tapestri is the only commercialized multi-omics platform capable of analyzing DNA and protein simultaneously from the same sample at single-cell resolution. The Tapestri Platform is being utilized by customers at leading research centers, pharmaceutical, and diagnostics companies worldwide to develop treatments and eventually cures for cancer.

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