Category Archives: Cell Biology

Organoids: Exploring Liver Cancer Initiation and the Possibilities of Personalized Glioblastoma Treatment – Technology Networks

April 29, 2020 medical

In the search for improved and high-throughput in vitro models, organoids have emerged as a promising 3D cell culture technology.1 Defined as a three-dimensional multicellular in vitro tissue construct, organoids are derived from cells that spontaneously self-organize into properly differentiated functional cell types to mimic at least some function of an organ.2 Organoid formation is driven by signaling cues in the extracellular matrix and medium, and is influenced by the particular cell types that are present.2 Compared with two-dimensional cultures, organoids incorporate more physiologically relevant cell-cell and cell-matrix interactions, and are a better reflection of the complex network found in vivo.With significant opportunities for studies of human-specific disease mechanisms, personalized medicine, drug discovery, pharmacokinetic profiling and regenerative medicine, organoids are being pursued across a range of disciplines. Many anticipate that these cell culture models will result in more efficient translation of research into clinical success. In this article, we explore the various types of organoids under development and shine a spotlight on some of the different approaches to organoids in cancer research.

Organoids can be derived from pluripotent stem cells (including embryonic stem cells or induced pluripotent stem cells) or neonatal or adult stem cells from healthy or diseased tissue.1,2 Cancer organoids have been generated from a range of human cancer tissues and cell lines including colon, pancreas, prostate, liver, breast, bladder and lung.6-12 This year, a research group led by Hongjun Song, Professor of Neuroscience at the Perelman School of Medicine at the University of Pennsylvania, published a report in Cell detailing methods for the rapid generation of patient-derived glioblastoma organoids.13Fresh tumor specimens were removed from 53 patient cases to produce microdissected tumor pieces that could survive, develop a spherical morphology and continuously grow in culture for at least two weeks (Figure 1). The production of glioblastoma organoids was achieved while maintaining a high level of similarity between the organoids and their parental tumors, with the expression levels of specific markers showing stability over long-term culture (48 weeks). Importantly, native cell-cell interactions were preserved by avoiding mechanical and enzymatic single-cell dissociation of the resected tumor. As Song explains, this was achieved on a clinically relevant timescale: Normally, the treatment for glioblastoma patients starts one month after surgery. The idea is that glioblastoma organoids can be generated within two weeks and subjected to testing of different treatment strategies to come up with the best option for a personalized treatment strategy.

Figure 1: Glioblastoma organoid generation, from fresh tumor pieces to frozen spherical organoids. Image used with permission from Jacob et al. 2020.One concern with organoid formation and expansion is the potential variability of the serum or Matrigel that can exist across batches and sources, creating variable exogenous factors that could cause the organoid to divert. This ultimately compromises reproducibility, a major bottleneck of current organoid systems.2,13 To avoid this source of error, Songs group used an optimized and defined medium devoid of variable factors that could contribute to the clonal selection of specific cell populations in culture.Glioblastoma is the most prevalent primary malignant brain tumor in adults,14 and having glioblastoma organoids available for research would present significant opportunities, explains Song: They can be used to test different drugs based on mutation profiles and to investigate mechanisms underlying tumor progression, drug sensitivity and resistance. While the accuracy of these predictions would need to be verified, researchers hope that patient-derived organoids will be used to help inform oncologists, accelerate drug discovery, and lead to better clinical trial design.Live-Cell Monitoring: Optimizing Workflows for Advanced Cell Models

As cell-based assays become technically more complex, the need to holistically capture dynamic and sometimes subtle cellular events becomes ever more important. By providing real-time imaging data of cellular events without disturbing the sample during the cell culture workflow, live-cell monitoring can support the optimization of these advanced models. Download this whitepaper to discover how live-cell monitoring can support such optimization, with a breadth of applications.

Ludwig Oxford Director Xin Lu Elected to the Royal Society – Newswise

April 29, 2020 medical

Newswise APRIL 29, 2020, New YorkLudwig Cancer Research extends its congratulations to Xin Lu, director of the Oxford Branch of the Ludwig Institute for Cancer Research, on her election to the Fellowship of the Royal Society.

Lu is recognized by the Royal Society for her significant contributions to the cell biology of cancer, particularly her work on the regulation of p53, a tumor suppressor protein whose inactivation or mutation contributes to the progression of a wide variety of tumor types. Early in her career, Lu explored how p53 induces cell suicide, or apoptosis, in response to the expression of cancer-driving genes and events such as DNA damage. That work led to the discovery by Lus group of the ASPP family of proteins, which control p53 activity and thus play a critical role in cancer biology. Aside from opening new approaches to the treatment of cancer, Lus continuing exploration of those proteins has exposed their role in other disorders, including sudden cardiac death and brain abnormalities.

Founded in 1660, the Royal Society is a fellowship of eminent scientists, engineers and technologists in the UK and the Commonwealth whose mission is to recognize, promote, and support excellence in science and to encourage the development and use of science for the benefit of humanity. It counts among its Fellows and Foreign Members some 80 Nobel Laureates, including Ludwig Oxfords Sir Peter Ratcliffe, a co-recipient of the 2019 Nobel Prize in Physiology or Medicine.

I am very honored to be named a Fellow of this historic Society, said Lu. I am grateful to Ludwig for its unwavering support for my research, and to the many mentors and collaborators who have helped me so much over the course of my career. Most important of all, my deep gratitude goes to the fantastic scientists in my laboratory, and colleagues Ive had the privilege to work with throughout my career to date, without whom this recognition would not have been possible.

Lu has directed Ludwigs Oxford Branch since it was established in 2007. In addition to her Ludwig post, she is a Professor in the Nuffield Department of Medicine at the University of Oxford. Lu is also a Fellow of the Academy of Medical Sciences and the Royal Society of Biology, a Fellow by election of the Royal College of Pathologists and a member of the European Molecular Biology Organization.

About Ludwig Cancer Research

Ludwig Cancer Research is an international collaborative network of acclaimed scientists that has pioneered cancer research and landmark discovery for nearly 50 years. Ludwig combines basic science with the ability to translate its discoveries and conduct clinical trials to accelerate the development of new cancer diagnostics and therapies. Since 1971, Ludwig has invested $2.7 billion in life-changing science through the not-for-profit Ludwig Institute for Cancer Research and the six U.S.-based Ludwig Centers. To learn more, visit http://www.ludwigcancerresearch.org.

For further information please contact Rachel Reinhardt, rreinhardt@lcr.org or +1-212-450-1582.

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Ludwig Oxford Director Xin Lu Elected to the Royal Society - Newswise

Cell Biology

One in Three Study Subjects Test Positive for COVID-19 Antibodies in MA – The Great Courses Daily News

April 29, 2020 medical

By Jonny Lupsha, News Writer

According to The Boston Globe, the new data about coronavirus exposure comes from a blood test led by Massachusetts General Hospital. Nearly one-third of 200 Chelsea residents who gave a drop of blood to researchers on the street this week tested positive for antibodies linked to COVID-19, the article said. Of the 200 random participants, 64 tested positive for the antibodies that are generated to fight the disease.

Antibodies are produced by our bodies immune systems as part of the bodys natural defense mechanism. They are often involved in cancer therapies.

Antibodies help fight off foreign agents that enter our bodies. In order to do this, the body needs to identify the enemy. According to Dr. David Sadava, Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center, any foreign agent that antibodies attack is called an antigen, in which anti stands for antibody and gen stands for generate. Theyre called antigens specifically because they generate antibodies.

Antigens are not necessarily a large substance, but its a group of atoms linked together in a specific way, Dr. Sadava said. The atoms on, for example, a toxin from a bacterium, like the botulinum toxin, have a unique shape. Some of those are atoms that we dont have in our bodiesonly the bacterium has itso the immune system will recognize that.

How are they recognized? Dr. Sadava said that a type of helper cell in your body called a T-cell recognizes the antigen as being a foreign agent. Essentially, the T-cell is always on the lookout for natural and foreign elements in the body. When it flags an antigen, it sets off a specific two-step response to it that includes both itself and antibodies.

In the first step of the immune response, when the body has been notified of an antigen, cells in the blood serum itself make antibodies against that antigen, if its in the blood. The antibodies mobilize in order to find and bind to the antigen specifically.

Dr. Sadava said this binding is like a lock and key. Antibodies have specific three-dimensional structures, and they will bind to any of the antigen thats in the blood system.

Antibodies can basically escort the antigen out of the body and stop it from causing any trouble along the way. If youre thinking of a bouncer in a nightclub, youre not far off.

The second step of the immune response happens on the cellular level. T-cells can kill some antigens. Dr. Sadava used a surprising example to illustrate how this overall process works.

You have antibodies made in small amounts, and T-cells made in small amounts, that recognize HIV, the virus that causes AIDS, he said. You have a small number of those soldiers that are constantly being made in small numbers. And if you are infected with HIV, all of a sudden, that army gets expandedit gets expanded when this recognition event happens, and all of a sudden those cells will be mobilized.

Once mobilized, the recognizing cells send signals to their siblings to divide and clone themselves to reject or kill cells that contain the antigen.

The residents of Chelsea tested positive for certain antibodies that their bodies made specifically to fight the coronavirus. This means that if they didnt have the coronavirus at the time of the test, they had already encountered it at some point in the past. If they hadnt, those specific antibodies wouldnt be in their blood.

Dr. David Sadava contributed to this article. Dr. Sadava is Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center. He earned a B.S. with first-class honors in biology and chemistry from Carleton University and a Ph.D. in biology from the University of California, San Diego.

Cell Biology

What do soap bubbles and butterflies have in common? – Jill Lopez

April 29, 2020 medical

Edith Smith bred a bluer and shinier Common Buckeye at her butterfly farm in Florida, but it took University of California, Berkeley, graduate student Rachel Thayer to explain the physical and genetic changes underlying the butterfly's newly acquired iridescence.

In the process, Thayer discovered how relatively easy it is for butterflies to change their wing colors over just a few generations and found the first gene proven to influence the so-called "structural color" that underlies the iridescent purple, blue, green and golden hues of many butterflies.

Her findings are a starting point for new genetic approaches to investigate how butterflies produce intricate nanostructures with optical properties, which ultimately could help engineers develop new ways to produce photonic nanostructures for solar panels or iridescent colors for paints, clothing and cosmetics.

Structural color is different from pigment color, like that in your skin or on a canvas, which absorbs or reflects different colors of light. Instead, it comes from light's interaction with a solid material in the same way that a transparent bubble develops a colorful sheen. The light penetrates it and bounces back out, interfering with light reflected from the surface in a way that cancels out all but one color.

At the Shady Oak Butterfly Farm in Brooker, Florida, Smith's breeding experiments with the Common Buckeye (Junonia coenia) -- a mostly brown butterfly with showy, colorful spots, found throughout the United States and often raised by butterfly farmers for butterfly gardens or wedding ceremonies -- were ideal for Thayer's study of structural color.

"Edith noticed that sometimes these butterflies have just a few blue scales on the very front part of the forewing and started breeding the blue animals together," said Thayer, who is in UC Berkeley's Department of Integrative Biology. "So, effectively, she was doing an artificial selection experiment, guided by her own curiosity and intuition about what would be interesting."

In a paper appearing online today in the journaleLife, Thayer and Nipam Patel, a UC Berkeley professor of molecular and cell biology who is on leave as director of the Marine Biological Laboratory in Woods Hole, Massachusetts, describe the physical changes in wing scales associated with Smith's experiment on the Common Buckeye, and report one genetic regulator of blue iridescence.

"I especially loved the clear evolutionary context: being able to directly compare the 'before' and 'after' and piece together the whole story," Thayer said. "We know that blueness in J. coenia is a recent change, we know explicitly what the force of selection was, we know the time frame of the change. That doesn't happen every day for evolutionary biologists."

Structural color produces showy butterflies

According to Thayer, hundreds of butterflies have been studied because of the showy structural color in their wing scales. The showiest is the blue morpho, with 5-inch wings of iridescent blue edged with black. Her study, however, focused on a less showy genus,Junonia, and found that iridescent color is common throughout the 10 species, even the drab ones. One unremarkable light gray butterfly, the pansyJ. atlites, proved under a microscope to have iridescent rainbow-colored scales whose colors blend together into gray when viewed with the naked eye.

One major lesson from the study, she said, is that "most butterfly patterns probably have a mix of pigment color and structural color, and which one has the strongest impact on wing color depends on how much pigment is there."

Thayer raised both the wild, brownish Common Buckeye and the cross-bred, bluer variety obtained from Smith. Using a state-of-the-art helium ion microscope, she imaged scales from the wings to see which scale structures are responsible for the color and to determine whether the color change was due to a change in structural color, or just a loss of brown pigment that allowed the blue color to stand out.

She found no difference in the amount of brown pigment on the scales, but a significant difference in the thickness of chitin, the strong polymer from which the scale is built and that also generates the structural color. In the wild buckeye, the thickness of the chitin layer was about 100 nanometers, yielding a golden hue that blended with the brown pigment. The bluer buckeye had chitin about 190 nanometers thick -- about the thickness of a soap bubble -- that produced a blue iridescence that outshined the brown pigment.

"They are actually creating the color the same way a soap bubble iridescence works; it's the same phenomenon physically," Thayer said.

She also found that, though the scales from theJunoniabutterflies have an elaborate microscopic structure, structural color comes from the bottom, or base, of the scale.

"That is not intuitive, because the top part of the scale has all of these curves and grooves and details that really catch your eye, and the most famous structural colors are elaborate structures, often in the top part of the scale," she said. "But the simple, flat layer at the bottom of the scale controls structural coloration in each species we checked."

"The color comes down to a relatively simple change in the scale: the thickness of the lamina," said Patel. "We believe that this will be a genetically tractable system that can allow us to identify the genes and developmental mechanisms that can control structural coloration."

Thayer also investigated the scales of mutant buckeyes created by Cornell University researchers that lacked a key gene, called optix, that controls color. The micrograph images demonstrated that lack of the gene also increased the thickness of the thin film of chitin in the scales, creating a blue color. Optix is a regulatory gene that controls many other butterfly genes, which Thayer will be looking at next.

"One thing that I thought was cool about our findings was seeing that the same mechanism that has recurred over millions of years of butterfly evolution could be reproduced really rapidly in (Smith's) artificial section experiment," she said. "That says that color evolving by changes in lamina thickness is a repeatable, important phenomenon."

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What do soap bubbles and butterflies have in common? - Jill Lopez

Cell Biology

From Nebraska’s Fields To The Ocean’s Floor: The Long Road Of Evolutionary Biologist Elma Gonzlez – Women You Should Know

April 29, 2020 medical

There is a theory that curiosity originates in leisure, that only after one has taken care of the big important things like food and shelter can one spare the mental room for questions like what a sixth dimensional sphere looks like or how lemurs got that way. Successful scientists, so the story goes, need space in their youth, long parent-subsidized hours to grapple with thorny mathematical and chemical topics so that their minds are primed for thinking on the highest level when a university education is tossed gently in their outstretched arms. If we are to spend money on science education, so the theory canters to its conclusion, we must spend it on developing programs for the respectable and dependable offspring of the middle class, whose lives and minds stand ready to make use of it.

At this point, counterexamples are doubtlessly flying to your fingertips for enumeration a list of What Abouts from the scientific pantheon featuring figures who worked their way up from nothing to achieve something of lasting value for humanity, but as for me Ive only ever needed one Elma Gonzlez. She came from the center of a grinding maw of economic, racial, gender, and social disadvantages, and not only survived their concentrated effects throughout her theoretically most formative intellectual years, but rose on the strength of her own determination and innate skill to shine a light on global-scale chemical processes that will shape our collective future.

Born in Mexico in 1942 to migrant workers, Gonzlez came to the United States at the age of six, did not attend school until the age of nine, and was at thirteen initiated into the life of the migrant farmer. That year, her father accepted the offer of a Mr. Manuel Flores to join his regular summer route through the Midwest, offering their services to an array of farmers along the way. It was back-throttling work, using a variety of wicked tools (including the dreaded, and now banned, cortito), while crouching in a variety of unregulated pesticides, paid by the acre rather than by the hour, and thus done at a pace that made no accommodation for a childs strength or stamina. Living conditions varied from farm to farm if the workers were lucky, they were put up in an old unused lodging on the property, if not they might find themselves crammed together in the loft of the pig sty, or huddled together with dozens of other migrant workers in hot temporary shelters with paper-thin walls.

Elma Gonzlez rose on the strength of her own determination and innate skill to shine a light on global-scale chemical processes that will shape our collective future.

As bad as the experience on the farms was, however, it was the trek from farm to farm, and the long return trip to Texas, that perhaps took the greatest toll. Traveling in the back of a truck for hours at a time with no bathroom breaks under a tarp that trapped heat in the sun and let in water in the rain, sleeping on thin bed rolls and under thinner mattresses by the side of the road, young Gonzlez was regularly exposed to the elements as well as the prejudices of local police who wanted nothing more than to see their caravan pack up and continue moving down the road, into the next county.

For years, this was her life, kneeling in fields and shuddering under a roadside blanket during the summer before returning to Texas, often weeks into the new school year, to catch up as best she could in her studies. If one good thing came of the hardships of her early life, it was the determination that she would, somehow by the force of her mind, find a way out of the migrant labor system. In 1961, her family stopped making the annual northern migrant labor loop to concentrate on Texas cotton harvesting work, and with all members of the family relatively grown and making money, Gonzlezs family could afford to accede to her earnest request to be allowed to go to college.

Gonzlez attended Texas Womans University as a double biology and chemistry major and even had the opportunity to intern one summer at the Baylor University College of Medicine. To make money straight out of college in order to help support the rest of her family, she took for three years a position as a research technician at the Southwestern Medical School of the University of Texas. While the position taught her some important fundamentals of laboratory technique, it was not advancing her real knowledge base in a way that would allow her to ever be anything but a technician.

She decided to apply to graduate schools in 1967 and was eventually accepted by Rutgers University, where she was pushed to excel by the tough-but-fair cellular biologist Charlotte Avers, the author of a standard text on molecular cell biology (called, in the true spirit of science, Molecular Cell Biology) and another on basic cell biology (called, yes, Basic Cell Biology). Here, Gonzlez began vectoring herself towards the study of cellular chemical processes that would define her career, and after post-doc work at UC Santa Cruz in 1972, she was offered an assistant professorship at UCLA in 1974.

Though she remained at UCLA for decades doing her foundational studies of algae calcification, her start there was a rocky one. She was hired primarily to fulfill a minority quota, and on arrival nobody knew precisely what to do with her, or where to put her. She didnt have an office or equipment, and ended up having to scrounge a free space among the mouse cages of the universitys vivarium in between rounds of trying to cut deals on discounted demonstration models of lab equipment so she could begin her research. After that rough start, her situation improved considerably when rubisco researcher Sam Wildman heard of her predicament and offered to share his lab space with her.

She had a place to work, and by 1993 was confirmed as a full professor on the strength of her ongoing work with coccolithophorid algae. These are major players in the global carbon cycle, and one of the great questions is how our rapidly changing climate will affect them and, in turn, their ability to scrub carbon dioxide from our atmosphere. Her work centered around the mechanisms that allow different strains of this algae to obtain carbon from water and lock it into calcium carbonate deposits which settle harmlessly to the bottom of the ocean.

Non-organic carbon in seawater, it turns out, is found more in dissolved HCO3 than carbon dioxide. The algae that Gonzlez studied take that HCO3 and combine it with calcium to make calcium carbonate, which traps one carbon, and carbon dioxide, which the algae uses for photoshynthesis. This process, however, also produces protons which need to be pumped out of the cell to avoid reaching toxic levels. If, however, seawater becomes too acidic, it will interfere with the ability of these algae to get rid of their steadily accumulating protons, which will in turn affect their ability to sink atmospheric carbon to the oceans floor.

Gonzlez theorized that the acidification of the oceans will have an impact on the evolutionary advantage that calcifying algae receive from their ability to use the relatively more abundant levels of oceanic HCO3 to feed their photosynthesis, and as a result might remove one of the global carbon cycles most steadfast components. Its a wonderful example of how something as simple as a chemical reaction can, when understood in its various biological guises, become a key clue in grasping the large-scale forces that govern our tenuous grasp upon existence on this planet, and it was gifted to us by a person whose value was, for a long lean decade, measured primarily in the amount of manual labor that could be wrung from her while still a child.

Perhaps there is something to be learned in that.

FURTHER READING:Gonzlez was a co-founder of the Society for Advancement of Chicanos/Hispanics & Native Americans in Science (SACNAS) in 1973 and is the first person featured in the 2008 Paths to Discovery: Autobiographies from Chicanas with Careers in Science, Mathematics and Engineering published by the UCLA Chicano Studies Research Center Press. SACNAS also has a small memoir that she wrote on her life which you can find here.

Lead image credit: Dr. Elma Gonzlez; By SACNAS Own work, CC BY-SA 4.0, via Wikimedia Commons

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From Nebraska's Fields To The Ocean's Floor: The Long Road Of Evolutionary Biologist Elma Gonzlez - Women You Should Know

Cell Biology

A Q&A With Josh Wolfe of Lux Capital – Morning Brew

April 29, 2020 medical

Lux Capital has backed many of the familiar startup faces in Emerging Tech Brew. Today, the VC firm is launching a new season of Futura, its web series exploring the operations of portfolio companies. Futura S2 includes startups like Anduril, Cala Health, and Saildrone.

Emerging Tech Brew recently caught up with Lux cofounder Josh Wolfe to discuss these investments and more. Note: This interview has been edited for clarity and length.

Thinking about the new season of Futura, why is storytelling an effective way to highlight the projects your portfolio companies are working on?

I think you know this from what you do on a daily basis, but we are storytelling creatures and social primates. Futura tells the stories of the individuals, mavericks, and scientists we like to celebrate and invest in, who believe something that everyone else doesnt believe. Or the guy or girl with a chip on their shoulder and something to prove.

In general, having trusted insider access to people who are quite literally inventing the future is special. Being able to asymmetrically bring that to the masses is the motive for why we do it.

Whats it like researching, investing, and doing diligence in companies that, as you say are, inventing the future?

On the one hand, Im always quite envious of people who have those early revenue metrics and can say heres where well be in a quarter or year later. Oftentimes when we're investing, we like to say that we believe before others might understand, so that has us investing in the cutting-edge.

Were constantly assessing the people first and foremost. Are they for real or full of shit? Thats the number one thing we have to assess early on. Its really hard to know at the moment of inception whether someone is delusional or visionary, if theyre a huckster or someone thats going to go change the world.

Take the person coming out of their garage saying they have some new flux capacitor. Were going to treat that very skeptically, versus a PhD whos highly esteemed by their peers, has lots of polished academic research, and a commercial instinct. Thats way more credible.

How about evaluating or validating the technology itself?

The Lux team is very diverse and very technical, with backgrounds in neuroscience, electrical engineering, mechanical engineering, stem cell biology, and material science. But every technology reveals our own ignorance, so then the most important question is: Does it work?

Its amazing how many investors will invest in something and then become pot-committed. Its the worst kind of psychological biascommitment bias. We ask: How much money accomplishes what, in what period of time, and who will care? Theres usually an Oh wow, holy shit moment where we get very excited to double down. Thats when we go from putting millions of dollars to tens of millions of dollars or more into a company.

When you have that feeling that invokes the Arthur C. Clarke quote [Any sufficiently advanced technology is indistinguishable from magic], thats the greatest risk-reducer of all.

What else is a key differentiator for Lux?

One part humility, one part paranoia. Theres a phenomenon I call 100-0-100. Its a cute way of saying with 100% certainty well be investing in the most cutting-edge stuff people can imagine over the next two years. Zero certainty what those things will actually be. Thats the intellectual honesty. The last 100% is the confidence of where we will find the next investments, which is at the edge of our already cutting-edge companies. One leads to the next one, which leads to the next one.

I hadn't really thought about the tech crossover between startups working on very different problems.

When we invest in one company, it can lead to knowledge that lets us find others. A priori, you never know what the second or third company will be. But just by having a sufficient amount of paranoia and curiositythe confidence of staying at the cutting-edge on this treadmill thats always picking up a bit fasterthat can lead you to the next company.

VC is the only asset class where you can get legal inside information about whats happening. You start to see white space and whos entering it.

Take Cala from Season 2. In CTRL-labs case from Season 1, youre reading from the brain using pretty sophisticated software, sensors, and machine learning. Youre reading what the brain intends to do; its more about intention capture. Cala is the opposite. How do we take the same wrist worn device and instead of reading from the brain write to the brain? How do we take people with essential tremors and through a device give them the stability of motions we all take for granted? Theyre helping restore dignity to someone that suffers, through technology.

Lets unpack a term you use frequentlydirectional arrows of progress. Can you explain that a bit?

Technologies are directionally predictable. The hardest thing to predict is the social piece of a technology. Its not what happens when one person has a phone, its when everyone does. Right now, you can see that with e-commerce, videoconferencing, and online learning.

As for technological arrows of progress, Im a big student of history. I like looking at how technology evolves. There's a directional arrow of progress that reduces entropy. Theres more information content in the next device. Theres less waste. It tends to be more efficient, a higher density per unit of raw material.

Transportation is an example. We went from horses to horse drawn carriages to cars to electric cars to an autonomous car. Were not going back to horses.

Now lets pivot to our current situation. How exposed are your portfolio companies to the coronavirus?

Ill start with the macro and then give you a post-pandemic prescription. Macro, everybody is suffering in some way. Its more than an economic or medical crisis; its a human crisis.

On a more technical and practical matter, weve always been more on the bearish side of things. Its this weird dichotomy where were ebullient optimists about the future but were generally very skeptical about human nature and markets, which are a collective of human nature. Were always admonishing our companies with this line: Failure comes from a failure of imagination.

So theyve been admonished to have rainy day money, expect the worst, and plan for bad scenarios. Now, we never prophesied a pandemic [editors note: us as well], but Ive been amazed at how quickly and swiftly theyve acted. Of the 130 companies we have, Ive seen five where they had financing that was going to close, or was at risk of closing, where the business wasnt going that well. They were likely to succumb.

Weve also seen some companies that have dropped everything to help. Shapeways has been shipping over 10,000 PPE to 10 different NYC hospitals. Desktop Metal is helping produce swabs for testing. It showed in a crisis how you can go from centralized manufacturing to distributed and do it in a very agile fashion.

I know you started as an expert in nanotech. What should our younger readers (potential future entrepreneurs and investors) be focused on? Should students or early-stage career folks focus on going really, really deep on something technical or scientific theyre passionate about?

I think the best thing that can serve you is science and technology. Id read everything Kevin Kelly ever wrote. A good understanding of human nature and psychology also helps. When our companies do or dont succeed, its because of the people. Its never because the technology didnt work.

Anywhere there are structural barriers and therefore competitive advantage is really important to identify. Id emphasize understanding the great competitors and clever things they did to make it harder to compete with them. Some of the greatest entrepreneurs have always been very thoughtful about that. And you yourself have to have a competitive advantage.

Any area we go into, its good to become obsessive. That way, when youre talking to someone with a PhD whos super technical, theyll take you seriously. I knew nothing about brain machine interfaces or nuclear but then became obsessed.

What science fiction are you currently obsessed with?

Currently, I think Chinese science fiction is sweeping and sophisticated. Its rooted in physics, computer science, and astronomy. Its not fantasy. Also the new William Gibson book, Agency. That was outstanding because its a real near-term prognostication of how technology is likely to evolve. A version of Black Mirror.

The gap between sci-fi and when it becomes real is just getting shorter and shorter.

Originally posted here:
A Q&A With Josh Wolfe of Lux Capital - Morning Brew

Cell Biology

Silver Bullet Water Treatment’s Taylor Robinson Appointed to Two Influential Cannabis Industry Advisory Committees – Yahoo Finance

April 29, 2020 medical

GOLDEN, Colo., April 29, 2020 /PRNewswire/ -- Silver Bullet Water Treatment, LLC today proudly announced that the Company's Manager of R&D and Analytical Services, Taylor Robinson, has recently been appointed to an advisor role on two influential cannabis industry standards committees.

Taylor will serve with distinction on the Cannabis Certification Council's (CCC) "Organically Grown Cannabis" Technical Advisory Council and ASTM International's Cannabis Best Management Standards Committee. Both committee appointments for Taylor will give Silver Bullet Water Treatment a significant voice in crafting the Best Management Practice standards for the burgeoning cannabis industry.

"Silver Bullet Water Treatment wishes to express the Company's sincere gratitude to CCC and ASTM for taking leadership on these important cannabis industry matters," said Silver Bullet Water Treatment CEO Brad Walsh. "Silver Bullet Water Treatment and these two organizations are committed to building strategic partnerships and promoting cooperation to provide the best guidance for a healthy future for the cannabis industry."

The CCC is a nonprofit standard holding body focused on providing consumer and industry education, transparency and choice in the cannabis industry. CCC is a leading advocate for clean, ethical and sustainable business practices in the cannabis industry. As a CCC Organically Grown Cannabis Technical Advisory Committee member, Taylor will advise the CCC on the development of production standards to define and certify cannabis as "CCC Organically Grown Cannabis." Primary goals of the CCC Committee include drafting core standards to grow organic cannabis, labelling requirements, testing procedures and compliance processes.

ASTM International is an international standards organization that develops and publishes voluntary consensus technical standards for a wide range of materials, products, systems, and services. As a member of ASTM's Cannabis Best Management Standards Committee, Taylor's activities will help the organization address quality and safety for the cannabis industry through the development of voluntary consensus standards. Subcommittees on which he may serve focus on the development of test methods, cultivation, quality assurance, laboratory considerations, packaging and security.

Taylor, who is the Research & Development Manager and Chief Chemist for Silver Bullet Water Treatment with expertise in molecular and cell biology, general water chemistry and microbiology, looks forward to his new advisory roles on behalf of the cannabis industry. "Taking a leading role with these advisory committees to pioneer the establishment of cannabis industry standards will be a challenge I and Silver Bullet Water Treatment look forward to meeting."

CEO Brad Walsh believes Silver Bullet Water Treatment's role as an industry advisor is only beginning. "Providing consultation, education and industry leadership on best management practices for cannabis cultivation and water use has been a driving force behind Silver Bullet Water Treatment's outsized impact on the cannabis industry. Taylor and Silver Bullet Water Treatment look forward to helping these excellent organizations create effective cannabis industry standards that will be relied on by cultivators/operators, the supply chain, governments, and utilities long into the future," said Walsh. "The addition of Taylor's expertise to the CCC and ASTM committees confirms Silver Bullet Water Treatment's increasingly influential voice in the cannabis, controlled environment agriculture and horticulture sectors."

About Silver Bullet Water Treatment

Established in 2011, Silver Bullet Water Treatment, LLC TREATS WATER BETTER through our commitment to solve our customers water quality challenges through the engineering and installation of comprehensive water treatment solutions and services. Silver Bullet Water Treatment is inspired to develop and introduce innovative, progressive solutions and be recognized as a go-to knowledge resource for the industries we serve.

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Cell Biology

Cell-cultured and plant-based seafood: Will COVID-19 boost progression in the sector? – FoodIngredientsFirst

April 29, 2020 medical

29 Apr 2020 --- As the world learns to deal with the coronavirus pandemic, eating behaviors are already changing. The global population is projected to reach more than 9.8 billion by 2050, and with this comes the challenge to secure sustainable, nutritious and plant-friendly food supplies. With the interest in cell-cultured seafood making waves and theacceptance of meat grown in a lab taking off, could the COVID-19 crisis boost further progression in this burgeoning sector?

FoodIngredientsFirstspeaks with innovators in cell- and plant-based seafood, as the pandemic shines a light on new ways of consuming fish and meat, in a way which is deemed better for the planet and provides a flexible alternative during times of crisis. Many of the key players in this space also predict significant funding of companies in this sector throughout the year, with a sharpened focus on speed to market.

Experts have already predicted that demand for meat, poultry and seafood will increase substantially as the global population increases over the next several decades. Now, as the world faces the impacts of the coronavirus pandemic, we are seeing how fragile our food supply chain is and how critical it is for the US to utilize all technology at our disposal to support a flexible and secure food system that can continue to feed the world, a spokesperson for Alliance for Meat, Poultry & Seafood Innovation (AMPS Innovation) tells FoodIngredientsFirst.

Click to EnlargeExperts have already predicted that demand for meat, poultry and seafood will increase substantially as the global population increases over the next several decades.A silver lining?BlueNalu has touted cell-based food as a solution to food security since its inception, and along with sustainability and traceability, Lou Cooperhouse, President and CEO, sees a greater need for this additional food supply.

The COVID-19 pandemic has created a heightened awareness regarding the vulnerability of our planet, he says. Consumers are taking a closer look at current food systems, how our food is sourced, and how their food choices can make a difference.

With the uncertainties and challenges brought by COVID-19, a light is cast on the fragility of our food system, how rapidly supply and demand can become mismatched, the way consumers interact with and receive products can shift, and how the processes we depend on can be put at risk, comments Michael Selden, CEO and Co-Founder of Finless Foods, which harnesses cellular biology to develop new ways to produce nutritious, environmentally-friendly versions of fish and seafood products.

It definitely shows the importance of agility and ensuring a trusted supply that can be localized and decentralized. Cell-based seafood can be a strong tool moving forward for us to address these challenges in a new, innovative way to ensure a stable and secure food system that can react quickly to new phenomena, he tells FoodIngredientsFirst. If anything, now even more than ever, there is a strong case made for the development and support of this burgeoning industry.

For Kimberlie Le, Co-Founder at Prime Roots which makes alternative meats and seafood, made from a whole food protein from koji, grown in California the global health crisis will provide a silver lining for plant-based meat and seafood. There has been a growing awareness among the general population about the concerns with animal agriculture from human and environmental health perspectives.

Consumers are also interested in trying new things while at home and they are also looking for products that are cleaner and healthier and have better shelf-life and safety standards, according to Le. Plant-based products are much better positioned to serve these growing consumer demands than their animal-based counterparts, she notes.

The cultured and alternative seafood space has attracted significant investments in recent times and technologies show no sign of slowing down. From pioneering technology that grows shrimp meat in a laboratory to fish made from fungus technologies are breaching new realms of possibility.

2020 has already been a banner year for companies producing both plant-based and cell-based seafood products in terms of investments, details Cooperhouse of BlueNalu, who recently closed on a US$20 million Series A round of financing for cell-based seafood. Meanwhile, Gathered Foods, parent company of the Good Catch brand, recently closed a US$32 million Series B round for its plant-based products.Click to EnlargeThe cultured and alternative seafood space has attracted significant investments in recent times and technologies show no sign of slowing down. Above is an image of plant-based "lobster" from Prime Roots.

I believe that we will see significant additional funding of companies in this sector in 2020, and we will also see increasing announcements of partnerships with conventional multinational food companies which will provide infrastructure to support getting these products efficiently to market, explains Cooperhouse.

In the cell-based seafood sector, we will also see advancements in cost reduction and readiness for market launch. We are likely to also see progress at the federal regulatory level, that brings us all closer to commercialization and market launch. BlueNalu is planning a small market launch later in 2021, pending this regulatory approval, he continues.

A better catch?Cooperhouse is also anticipating that there will be a significant interest in cell-based seafood products from both consumers and foodservice operators. Cell-based seafood products originating from companies like BlueNalu provide an option that is sustainable, consistent, free of environmental contaminants, with 100 percent yield, that can dramatically reduce the stresses on our ocean and offer many more additional benefits, he stresses. We are also seeing increased interest in BlueNalus cell-based seafood as our process results in a more stable global supply chain and enhanced food security.

We need various tools in the toolbox to supply this growing demand in the near future, including well-managed wild-caught fisheries, responsible aquaculture, and, importantly, innovations in cell-based seafood, explains Selden of Finless Foods. Cell-based seafood provides an additional benefit for those species that are in high demand, such as tuna, and specifically Bluefin tuna, which have a strong conservation thesis.

Global demand for seafood is currently at an all-time high and is anticipated to increase significantly in the decades ahead, particularly as GDP increases in nations around the world. Unfortunately, says Cooperhouse, Our supply of seafood will be continually challenged to keep up with this demand, and there is great concern from many global organizations regarding our ability to feed our planet with its protein supply in the decades ahead.

Based on global protein consumption, BlueNalu expects that cell-based seafood products will make up a great majority of all cultured meat products during this time period and the company is building a library of species and seafood products to meet this growing demand.

Responding to waves of changeThe regulatory environment for the cell-based industry is in the process of being solidified,to ensure a clear, supportive regulatory pathway to market, explains Selden of Finless Foods. The biggest difficulty for cell-based seafood is reducing costs to an affordable level for consumers to access, he notes.

Meanwhile, developing stable cell lines in seafood without genetic engineering is deemed one of the biggest challenges in cell-cultured seafood, Chris Damman, Chief Technical Officer at BluNalu, tells FoodIngredientsFirst.

Click to EnlargePlant-based spicy "tuna" from Prime Roots. The company says plant-based seafood and fish are still lacking in the market.There were no fish muscle cell lines available worldwide when BlueNalu began operations in June 2018, he comments. As all of our products are non-GMO, and we had to develop new cell isolation methods and proliferation protocols.

Another challenge Damman details is developing growth media that are serum free and cost efficient. BlueNalus protocols eliminate the need for FBS (fetal bovine serum) in its large-scale production process. Instead, BlueNalu has developed proprietary formulations that enable us to grow our cells without serum, he states.

Meanwhile, the goal is to make a product that handles and cooks like conventional fish, he remarks. BlueNalu did just that and demonstrated this with yellowtail amberjack in December 2019. Our chef demonstrated that our yellowtail can be prepared in various ways, including deep frying and marination in an acidified solution [as in a poke or ceviche application]. Creating cell-based fish pieces that have the right consistency and mouthfeel in the raw state and when cooked is a technical milestone that is very difficult to accomplish, Damman explains.

Currently, BlueNalu is working on Mahi Mahi as the next species in the companys product pipeline. Within the next 12 months it will enter the product development phase where we fine-tune the texture and taste. This product will then be ready to enter a test market in the second half of 2021, once FDA regulatory clearance has been obtained, reveals Damman.

Turning the tide on plant-based seafoodAccording to Le at Prime Roots, plant-based seafood and fish are still lacking in the market, but she does expect there to be some new products and advancements in 2020. This is a largely underserved market, and some sources cite that 40 percent of the consumption of protein globally is in seafood while we know that less than 1 percent of alternative proteins are targeting seafood, she highlights.

Many players in the alternative meat space mostly use soy, wheat, or pea-based ingredients, while Prime Roots products are made using koji, a fermented Japanese fungus.

In terms of flavors and colors, there are a lot of innovative ingredients from plant and algae sources, notes Le, adding that there are many textures and flavors that are almost impossible to replicate with plant bases since they tend to be airy and spongy in texture and have strong off-flavors.

By Elizabeth Green

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Cell Biology

COVID-19: What’s RNA research got to do with it? – University of Rochester

April 29, 2020 medical

April 28, 2020

Rochester research into RNA structure and function provides key information for developing coronavirus treatments.

Viruses like the coronavirus that causes COVID-19 are able to unleash their fury because of a devious weapon: ribonucleic acid, also known as RNA.

A contingent of researchers at the University of Rochester study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. As COVID-19 continues to spread around the globe, RNA research provides an important foundation for developing antiviral drugs, vaccines, and other therapeutics to disrupt the virus and stop infections.

The Universitys website is a way to find guidance and critical information during a rapidly changing situation.

Find out what to do if you or a close contact have symptoms or think you may have been exposed.

Understanding RNA structure and function helps us understand how to throw a therapeutic wrench into what the COVID-19 RNA doesmake new virus that can infect more of our cells and also the cells of other human beings, says Lynne Maquat, professor of biochemistry and biophysics at the University of Rochester Medical Center and the director of Rochesters Center for RNA Biology.

In the past few decades, as scientists came to realize that genetic material is largely regulated by the RNA it encodes, that most of our DNA produces RNA, and that RNA is not only a target but also a tool for disease therapies, the RNA research world has exploded, Maquat says. The University of Rochester understood this.

In 2007, Maquat founded the Center for RNA Biology as a means of conducting interdisciplinary research in the function, structure, and processing of RNAs. The center involves researchers from both the River Campus and the Medical Center, combining expertise in biology, chemistry, engineering, neurology, and pharmacology.

While much of the research across the University has been put on pause, labs that are involved in coronavirus research remain active.

Our strength as a university is our diversity of research expertise, combined with our highly collaborative nature, says Dragony Fu, an assistant professor of biology on the River Campus and a member of the Center for RNA Biology. We are surrounded by outstanding researchers who enhance our understanding of RNA biology, and a medical center that provides a translational aspect where the knowledge gained from RNA biology can be applied for therapeutics.

In mammals, such as humans, DNA contains genetic instructions that are transcribedor copiedinto RNA. While DNA remains in the cells nucleus, RNA carries the copies of genetic information to the rest of the cell by way of various combinations of amino acids, which it delivers to ribosomes. The ribosomes link the amino acids together to form proteins that then carry out functions within the human body.

Many diseases occur when these gene expressions go awry.

COVID-19, short for coronavirus disease 2019, is caused by the novel coronavirus SARS-CoV-2. Like many other viruses, SARS-CoV-2 is an RNA virus. This means that, unlike in humans and other mammals, the genetic material for SARS-CoV-2 is encoded in RNA. The viral RNA is sneaky: its features cause the protein synthesis machinery of our cells to mistake it for RNA produced by our own DNA.

While SARS-CoV-2 is a new coronavirus, it likely replicates and functions similar to related coronaviruses that infect animals and humans, says Douglas Anderson, an assistant professor of medicine in the Aab Cardiovascular Research Institute and a member of the Center for RNA Biology, who studies how RNA mutations can give rise to human disease.

A graphic created by the New York Times illustrates how the coronavirus that causes COVID-19 enters the body through the nose, mouth, or eyes and attaches to our cells. Once the virus is inside our cells, it releases its RNA. Our hijacked cells serve as virus factories, reading the viruss RNA and making long viral proteins to compromise the immune system. The virus assembles new copies of itself and spreads to more parts of the body andby way of saliva, sweat, and other bodily fluidsto other humans.

Once the virus is in our cells, the entire process of infection and re-infection depends on the viral RNA, Maquat says.

Researchers Douglas Anderson, Dragony Fu, and Lynne Maquat are among the scientists at the University of Rochester who study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. (University of Rochester photos / Matt Wittmeyer / J. Adam Fenster)

Maquat has been studying RNA since 1972 and was part of the earliest wave of scientists to realize the important role RNA plays in human health and disease.

Our cells have a number of ways to combat viruses in what can be viewed as an arms race between host and virus. One of the weapons in our cells arsenal is an RNA surveillance mechanism Maquat discovered called nonsense-mediated mRNA decay (NMD).

Nonsense-mediated mRNA decay protects us from many genetic mutations that could cause disease if NMD was not active to destroy the RNA harboring the mutation, she says.

Maquats discovery has contributed to the development of drug therapies for genetic disorders such as cystic fibrosis, and may be useful in developing treatments for coronavirus.

NMD also helps us combat viral infections, which is why many viruses either inhibit or evade NMD, she adds. The genome of the virus COVID-19 is a positive-sense, single-stranded RNA. It is well known that other positive-sense, single-stranded RNA viruses evade NMD by having RNA structures that prevent NMD from degrading viral RNAs.

Maquats lab is currently collaborating with a lab at Harvard University to test how viral proteins can inhibit the NMD machinery.

Like Maquat, Fu studies fundamental aspects of RNAand has found that his research on proteins may, too, be applicable to coronavirus research.

Fus lab analyzes enzymes and proteins that modify the chemical structure of RNA and how these chemical modifications impact the function of RNA. A research group at the University of California, San Francisco, recently identified an interaction between a protein made by the SARS-CoV-9 virus and a protein Fu studies.

This is an intriguing result, and we are currently thinking of ways this interaction could affect the host cell, Fu says. There is emerging evidence that RNA-based viruses undergo RNA modification, so we could use this knowledge to identify key links between the host and pathogen for development of a coronavirus vaccine or treatment.

One of the reasons viruses are such a challenge is that they change and mutate in response to drugs.

Targeting viral RNA, or the proteins it produces, is key for treating this disease.

That means novel virus treatments and vaccines have to be created each time a new strain of virus presents itself. Armed with innovative research on the fundamentals of RNA, scientists are better able to develop and test therapeutics that directly target the RNAs and processes critical to a viruss life cycle.

The University of Rochester Medical Center, for instance, is currently participating in a clinical trial to evaluate the safety and efficacy of a potential coronavirus treatment called remdesivir, an antiviral drug particularly tailored to attack RNA viruses. The drug inhibits RNA polymerase, an enzyme responsible for copying a DNA sequence into an RNA sequence.

Anderson has found that alternative therapeutics, such as the gene-editing technology CRISPR, may additionally usher in a new approach to how we target and combat infectious diseases, he says.

For the past few years, Andersons lab has developed tools and delivery systems that use the RNA-targeting CRISPR-Cas13 to treat human genetic diseases that affect muscle function. CRISPR-Cas13 is like a molecular pair of scissors that can target specific RNAs for degradation, using small, programmable guide RNAs.

When the health crisis first became apparent in Wuhan, China, researchers in Andersons lab turned their focus toward developing a CRISPR-Cas13 therapeutic aimed at SARS-CoV-2. Applying the knowledge already available about coronavirus RNA replication, they designed single CRISPR guide RNAs capable of targeting every viral RNA that is made within a SARS-CoV-2 infected cell. Using a novel cloning method developed in Andersons lab, multiple CRISPR guide-RNAs could be packaged into a single therapeutic vector (a genetically engineered carrier) to target numerous viral RNA sites simultaneously. The multi-pronged targeting strategy could be used as a therapy to safeguard against virus-induced cell toxicity and prevent escape of viruses which may have undergone mutation.

Infectious viruses and pandemics seemingly come out of nowhere, which has made it hard to rapidly develop and screen traditional small molecule therapeutics or vaccines, Anderson says. There is a clear need to develop alternative targeted therapeutics, such as CRISPR-Cas13, which have the ability to be rapidly reprogrammed to target new emerging pandemics.

While many new treatments for the novel coronavirus are being considered, there is one thing that is certain, Maquat says: Targeting viral RNA, or the proteins it produces, is key for treating this disease.

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COVID-19: What's RNA research got to do with it? - University of Rochester

Cell Biology

Conclusion of an Agreement in Principle Between Bold Capital and Dymedso, a Corporation Involved in Lung Disease Treatment and Treating COVID-19…

April 29, 2020 medical

MONTREAL, April 29, 2020 (GLOBE NEWSWIRE) -- Peter Rona, President and Chief Executive Officer of Bold Capital Enterprises Ltd. (Bold) (TSX-V Bold), a Capital Pool Company, is pleased to announce the conclusion of an agreement in principle dated April 28, 2020 with Dymedso Inc. (Dymedso) for the realization of a qualifying transaction, as per Policy 2.4 of the TSX Venture Exchange (the Exchange).

About Dymedso

Dymedso is a medical device corporation using sound (acoustics) to treat patients with airway clearance issues. Its flagship product, the Frequencer V2x (the Frequencer), provides airway clearance therapy and promotes bronchial drainage by inducing vibration through chest walls. This medical device is intended to be a component of chest physiotherapy by providing a convenient airway clearance method without harsh external thorax manipulation. The Frequencer is indicated for patients who have respiratory ailments that involve defective mucociliary clearance, as typically seen in patients suffering from cystic fibrosis as well as Chronic obstructive pulmonary disease (COPD), bronchiectasis, ciliary dyskinesia syndromes, asthma, muscular dystrophy, neuromuscular degenerative disorders, postoperative atelectasis, and thoracic wall defects.

Dr. Laura McIntosh, Human Cell Biologist, sees a potential role for the Frequencer in the context of the COVID-19 crisis1: The majority of COVID-19 fatalities are the result of acute respiratory distress syndrome (ARDS). In a recent study in China, researchers performed autopsies on deceased patients and found large amounts of sticky mucus and hyaline membranes in the deep-seated airways. And clearing the smaller airways is precisely what the Frequencer does.

While controlled clinical studies on the effectiveness of the Frequencer on COVID-19 patients have not yet been done, more than 650 Frequencers are currently being utilized across the world to assist with airway recruitment and secretion removal. The technology is in use in clinical settings for COVID-19 treatment in Montral and in Germany.

The Frequencer has obtained FDA approval, Health Canada licenses, UL approval, and CE Mark. The Frequencer is approved for sale in the United States, the European Union, Canada and the Middle East. Dymedso is also ISO 13485 certified for the design manufacturing and maintenance of pulmonary medical devices.

Dymedso and Bold are not making any express or implied claims that its product has the ability to eliminate, cure, or contain the COVID-19 virus at this time.

Summary of the Terms of the Agreement in Principle

According to the terms of the agreement in principle, Bold proposes to acquire all the issued and outstanding securities of Dymedso by the issuance of common shares and, upon the closing of the acquisition, the shareholders of Bold and Dymedso will hold respectively 12% and 88% of all the issued and outstanding common shares of Bold, calculated prior to any additional financing. The qualifying transaction is subject to various conditions such as its approval by the board of directors of Bold and Dymedso, the hiring of a brokerage firm and the completion of a concurrent private or public placement of a minimum of $2,000,000 and a maximum of $5,000,000. The qualifying transaction constitutes an arms length qualifying transaction and is not subject to shareholder approval. Furthermore, the Exchange has not considered the merits of the contemplated qualifying transaction. A more detailed press release will be subsequently published in order to provide additional details on the contemplated qualifying transaction. Consequently, trading in the common shares of Bold will be halted until the publication of a press release announcing that trading in the common shares is resumed.

Further Details Regarding Dymedso

Based on the unaudited financial statements of Dymedso for the year ended September 30, 2019, Dymedso had total current assets of approximately $521,587, total current liabilities of approximately$808,988 and a shareholders equity of approximately $4,124,079. Dymedso has generated $671,000 in revenue, a gross margin of $292,328 and a net loss of $221,798. It is anticipated that Dymedso will be cash flow positive within a year with the financing mentioned above.

Mr.Yvon Robert holds, directly or indirectly, 11,993,733 shares in the capital of Dymedso, which represent an aggregate of 94.41% of the voting shares of Dymedso. To the knowledge of Bold and Dymedso, no other person will beneficially own, directly or indirectly, or exercise control or direction over, more than 10% of the voting rights attached to all of the outstanding shares of Bold after the completion of the proposed qualifying transaction.

Directors and Officers of Dymedso

Subject to applicable approvals, it is anticipated that four out of the five directors of Dymedso to be nominated will be Richard Boudreault, Kim Anderson, Simon Phaneuf and Yvon Robert. Management of Dymedso will include Kim Anderson as President, Richard Boudreault as Chief Executive Officer and Chairman of the Board, and Simon Phaneuf as Chief Scientific Officer. Biographies for the officers and directors of Dymedso are described below.

Richard Boudreault, FRSC, FCAE, FCMOS, HFRCGS, FCASI, FWAAS, FIAA, FinstP, AFAIAA, SMIEEE Chief Executive Officer of Dymedso

Richard Boudreault is the CEO of Dymedso. He joined Dymedso in January 2020 to bring it to another level. A successful award winning serial entrepreneur and C-level executive, Mr.Boudreault has held top corporate positions in organizations of all sizes in both the private and public sectors and has sat on over 30 boards. Over 40 years, he has led organizations across a variety of sectors including advanced materials, nanotechnology, photonics, resources and medical devices. He was involved with various publicly traded corporations in Canada including Orbite Technologies Inc. (ORT), ART Advanced Research Technologies Inc. (ARA) and 5N Plus Inc (VNP). Of the 12technology corporations he has led along the years, six have been sold to large conglomerates, four went public and two are within their growth phase.

He chairs the Board of the national polar agency, Polar Knowledge Canada and the R&D advisory Board of the National Optics Institute. Mr.Boudreault has been actively involved in venture capital portfolio management, notably for the Caisse de dpot et placement du Quebec in the areas of sustainable energy, new materials, and the medical and transport industries. He is the originator of more than 80 patents (standing and pending) split in a dozen of families and his passion for innovation keeps him active in the Canadian VC landscape as a consultant and investment committee member.

Mr.Boudreault holds a bachelors degree in applied physics, an MBA and a professional masters degree in engineering, which he earned at Cornell. He is an adjunct professor at cole polytechnique de Montral, where he teaches and performs applied research on environmental chemical engineering, green chemistry and clean tech innovation and is a visiting scholar at McGill University.

He is the holder of a number of prestigious national and international fellowships, was awarded the Queen Elizabeth II Diamond Jubilee Medal, was knighted into Frances Ordre des Palmes acadmiques, and is a recipient of the Canadian Association of Physicist Medal for Outstanding Service in Applied Photonics and the American Physics Societys George Pake Award for innovation management. He also received the Institute of Electrical and Electronics Engineers Lifetime career prize for Engineering in Medicine and Biology. All these prizes were obtained for his medical device industry and innovation expertise.

Kim Anderson President of Dymedso

KimAnderson is an experienced medical device executive. She is President of Dymedso. She joined the corporation in January 2017 as Sales and Marketing Director. With over 20 years or experience in sales, she has worked for multinational organizations in the dental industry including orthodontics, implantology and CAD/CAM technology.

Ms.Anderson holds a bachelors degree in marketing and communication from University of Montral. Her sales successes were directly linked to her customer-oriented selling approach and skills to establish effective strategies to facilitate the integration of innovative technologies to the dental workflow. She has won numerous sales awards such as Representative of the Year, for highest sales growth and for achieving sales goals for six consecutive years. Her experience in customer management, combined with solid technical experience, has allowed her to work with a wide range of specialists as well as university faculties, hospitals, private dental offices and dental laboratories. She was invited to lecture at several conferences and training, including the undergraduate program at University of Montral and continuous education programs for dentists and dental staff.

Ms.Anderson worked for four years in sales at Ormco, a dental corporation specializing in orthodontic appliances (Orange, California). She also held a sales position for two years at Nobel Biocare (Toronto, Canada) and she served as Executive Sales Manager for Dentsply Sirona Implants (Waltham, Massachusetts) from 2005 to 2016. The corporation focuses on implantable medical devices, integrated digital workflow, computer-aided design and computerized assisted manufacturing process.

Simon Phaneuf, MD, CCFP (EM) (SEM), dip. ABLM, MBA Chief Scientific Officer of Dymedso

SimonPhaneuf is the CSO of Dymedso. He joined the corporation in February 2020 to assist in the next stages of development. A Medical Doctor with extensive clinical and academic experience, he has also participated in several start-ups in medical and technological companies.

Dr.Phaneuf currently teaches medicine at Universit Laval and is a former Clinical Professor of Medicine at Universit de Sherbrooke. He is specialized in Emergency Medicine, Sports and Exercise Medicine, and Lifestyle Medicine. Throughout his career, he participated in numerous clinical trials and sat on the Ethics Board Committee at Charles LeMoyne Hospital for several years. He also developed several medical devices in the fields of emergency medicine and minimally invasive surgery and is co-author of several corresponding patents. These innovations are currently being used on a daily basis both in North America and in Europe.

His experience as executive includes implementation of ISO 13485 for design and production of medical devices as well as quality control systems compliant with the Canadian Food Inspection Agency requirements. He also sat on corporate boards and scientific advisory committees of both private and public companies.

Dr.Phaneuf holds a medical doctorate (MD) degree from Universit de Montral and a certificate of added competency in Emergency Medicine and in Sports and Exercise Medicine, as well as an executive MBA from Universit de Sherbrooke. He also happens to be the first physician in the Province of Qubec to be certified by the American Board of Lifestyle Medicine.

Yvon Robert Director

Yvon Robert graduated from the Universit de Sherbrooke in physical education. He has always been very involved in sports and cultural organizations in the region, either as president of the Qubec Games (les Jeux du Qubec) or as an event organizer. For several years, he was responsible for physical education programs at a school board and was a professor at the Universit de Sherbrooke.

He then became Director of Marketing for the Winnipeg Jets club (AHL) in the National Hockey League. Two years later, he joined the marketing department of the Montreal Canadiens hockey club where he created LES CANADIENS magazine and became its publisher.

In 1988, Mr.Robert incorporated Les Consultants C.O.R.P. Inc., a subcontracting company operating in the publishing industry.

In 2002, Mr. Louis Plante, a young cystic fibrosis patient, invented an acoustic airway clearance device and joined Mr.Robert to incorporate Dymedso Inc. After several years of clinical trials and research in acoustics at the Universit de Sherbrooke, it was finally in 2009 that Mr.Robert decided to take over the companys management and develop the Frequencer, a medical device that uses low frequency acoustic waves to dislodge mucus that accumulates in the lungs.

It took two years of development, design and certification to finally introduce the Frequencer in 2011.

Mr.Robert has recently stepped down as President of Dymedso to focus on the development of Dymedso's new products.

The scientific information contained in this news release was read and approved by Dr.Simon Phaneuf, CSO of Dymedso.

Completion of the transaction is subject to a number of conditions, including but not limited to, Exchange acceptance and if applicable pursuant to Exchange Requirements, majority of the minority shareholder approval. Where applicable, the transaction cannot close until the required shareholder approval is obtained. There can be no assurance that the transaction will be completed as proposed or at all.

Investors are cautioned that, except as disclosed in the management information circular or filing statement to be prepared in connection with the transaction, any information released or received with respect to the transaction may not be accurate or complete and should not be relied upon. Trading in the securities of a capital pool company should be considered highly speculative.

The TSX Venture Exchange Inc. has in no way passed upon the merits of the proposed transaction and has neither approved nor disapproved the contents of this press release.

Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in policies of the TSX Venture Exchange) accept responsibility for the adequacy or accuracy of this press release.

1 Dr.Laura McIntosh: Acoustic Airway Clearance with the FrequencerTM - Clinical Evidence and Markets (2020). To review this white paper, log on to: https://www.dymedso.com/wp-content/uploads/2020/04/White-paper-final-Apr-20-2020-signed-min-1.pdf

About Laura McIntosh, Ph.D.

Laura McIntosh is a biotech R&D leader with 15 years experience in the development and commercialization of innovative biological products and services for human health and agriculture. She has significant expertise in driving science and product development strategies, managing academic and industrial scientific collaborations, and intellectual property creation and management. Most recently, Dr.McIntosh was the Vice President R&D at Concentric AG where she was responsible for the science and IP strategy in the development of commercially viable microbial-based products for the soil microbiome. As Vice President, Translational Research at Caprion Biosciences, she was responsible for the scientific integrity and oversight of all client-based proteomics projects. She also co-led a large public-private personalized medicine project in the Province of Quebec (www.pmpc-org.com/en). Dr.McIntosh also held senior-level positions at Osprey Pharmaceuticals Ltd where she led the research and clinical trials of a platform of protein therapeutic drugs, and at ART Advanced Research Technologies where she was involved in the development and commercialization of an optical imaging device.

After completing her doctorate in human anatomy and cell biology at the University of Manitoba, Dr.McIntosh was awarded an NSERC postdoctoral fellowship at the National Research Council of Canada. Dr.McIntosh also holds a Master of Science in Human Anatomy and Cell Science from the University of Manitoba, and a Bachelor of Science in Zoology from Brandon University in Brandon, Manitoba. She has 28 peer reviewed publications and four patents.

Forward-Looking Statement

This press release includes forward-looking statements that are subject to risks, uncertainties and other factors, including the possibility of unfavourable results from clinical trials involving the Frequencer and the treatment of COVID-19 even if the Frequencer has been successfully used for the treatment of other lung diseases. As a result, the Frequencer may never be successfully commercialized for COVID-19. All statements other than statements of historical fact could be deemed forward-looking statements. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. All forward-looking statements are based on information currently available to Dymedso and Dymedso assumes no obligation to update any such forward-looking statements.