Category Archives: Gene Medicine

Azure pools rich in magnesium and calcium carbonate but low in phosphorus provide an ideal habitat for ancient bacterial reefs at Cuatro Cinegas, in theChihuahuan Desert of Mexico.

By Rodrigo Prez Ortega Jun. 30, 2020 , 3:40 PM

Valeria Souza Saldvar never planned to devote her life to a remote and ancient oasis more than 1000 kilometers north of her laboratory in Mexico City. But a call in early 1999 changed that.

Its one of the best cold calls Ive ever made, says James Elser, a limnologist at the University of Montana. He had picked up the phone to invite Souza Saldvar to join a NASA-funded astrobiology project in Cuatro Cinegasa butterfly-shaped basin with colorful pools, or pozas, in the middle of Mexicos Chihuahuan Desert.

Neither Souza Saldvar, a microbial ecologist at the National Autonomous University of Mexico, University City, nor her ecologist husband and research partner Luis Eguiarte Fruns, also at UNAM, had ever visited Cuatro Cinegas. That first trip convinced them to completely change their research plans. Looking at those mountains and the water, I fell in love, Souza Saldvar says.

The landscapemore than 300 turquoise-blue pozas scattered across 800 square kilometers, among marshes and majestic mountainswasnt the only draw. The waters, whose chemistry resembled that of Earths ancient seas, teemed with microbes; unusual bacterial mats and formations called stromatolites carpeted the shallows. When Souza Saldvar first cultured the organisms from the pozas, The amount of microbes was enormous, as was the diversity of colors and colony sizes, she recalls. For her, this remote microbial hot spot was an irresistible mystery.

Since then, work by Souza Saldvar, Eguiarte Fruns, and a widening circle of collaborators in Mexico and the United States has shown that Cuatro Cinegaswhich means four marshes in Spanishis one of the most biodiverse places on the planet. Theres nowhere that has so much ancient diversity of microorganisms, says Michael Travisano, an evolutionary ecologist at University of Minnesota, Twin Cities, who has collaborated with the Mexican researchers since 2001. Among the most recent additions to that menagerie are hundreds of species of archaea, the ancient microbes that may have given rise to eukaryotesorganisms with complex, nucleated cells.

At the Pozas Azules ranch in Cuatro Cinegas, about 100spring-fed pools dapple the desert. Each has a unique microbial and mineral composition.

The diversity includes strains with unusual adaptations, such as the ability to build their lipid membranes with sulfur instead of the usual phosphorus, which is scarce in the waters of thepozas. It includes potential sources of new compounds for medicine and agriculture. And it poses a question that has occupied Souza Saldvar and Eguiarte Fruns for the past 20 years: How did this Noahs Ark of ancient microbes arise? Its a dream for every biologist to know the origin of diversification, Souza Saldvar says.

But her dream might be short-lived. Since the 1970s, farmers have intensively drained water from thepozasand rivers to irrigate nearby fields of alfalfa, grown for cattle fodder, gradually drying the improbable oasis. Souza Saldvar has galvanized a conservation effort that has slowed the drainage; in the coming weeks, a canal that removes 100 million cubic meters of Cuatro Cinegass water annually is scheduled to close. In the meantime, the researchers have been trying to describe as much as they can, as fast as they can, before their belovedpozasdry up and the precious microscopic life that has survived undisturbed for millions of years dies off.

Cuatro Cinegasservedas a stopping point for hunter-gatherers for thousands of years. To date, 50 archaeological sites with cave paintingssome dating to 2275 B.C.E.have been found in mountain cavesaround the basin. Much later, the region made a mark on history when Venustiano Carranza, born in a village at the basins margin, became a leader of the Mexican Revolution and president of Mexico from 1917 to 1920. Nowadays, the village is called Cuatro Cinegas de Carranza after him.

But in the 1960s, Cuatro Cinegas started to become famous for its biodiversity, as biologists began to describe new species of snails, fish, turtles, and plants found in the pools and marshesand often nowhere else.

Wendell Minck Minckley, a renowned ichthyologist at Arizona State University (ASU), Tempe, was first lured to Cuatro Cinegas after learning thatthe worlds only aquatic box turtle(Terrapene coahuila) lived there. Over the years, Minckley made frequent trips to thepozas, describing their snails and fish (Herichthys minckleyi, a cichlid, bears his name) while making connections with the local people.

In the Cuatro Cinegas Basin, ringed with mountains and desert, an aquifer feeds hundreds of pools and marshes. But canals tapping water for agriculture threaten the wetlands and the biodiversity they host.

(MAP) N. DESAI/SCIENCE; (DATA) E. MAMER AND T. NEWTON/NEW MEXICO BUREAU OF GEOLOGY AND MINERAL RESOURCES; VALERIA SOUZA SALDVAR; NATIONAL COMMISSION OF NATURAL PROTECTED AREAS MEXICO

Minckley also noticed peculiar, rocky structures in the pools. They were stromatolites, biological structures normally found as fossils dating back as much as 3.5 billion years. Colonies of photosynthesizing bacteria, which boosted early Earths oxygen, created the layered formations by depositing carbonates and trapping sediment in ancient, shallow seas. But these stromatolites were alive. Also found in other extreme environments such as Australias warm, salty Shark Bay, living stromatolites are sort of a window into early Earth, Elser says. Thepozasalso nurture bacterial mats, a soft form of stromatolites normally found deep in the ocean.

As early as the 1970s, Minckley realized the pools and their diversity were under threat: Local farmers were carving canals to tap their water. Thanks in part to his lobbying, the Mexican government in 1994 designated an 85,000-hectare protected area. But the drainage continued. Minckley knew that Cuatro Cinegas was going to die, Souza Saldvar says. He thought NASA might be its salvation.

In 1998, NASA established its Astrobiology Institute, a network of researchers studying life in extreme environments that might resemble conditions on other planets. Minckley saw an ideal astrobiology study site in the waters of thepozas, with their seemingly inhospitable chemistry and living stromatolites. But he was no expert on extreme environments, so he enlisted Elser, who specializes in how water chemistry affects ecosystems and also works at ASU. After they submitted a 1998 proposal to fund the project, however, NASA said they should add experts on microbiology and evolutionand those experts had to be Mexican to help secure permits to obtain samples. Based on colleagues suggestions, Elser called Souza Saldvar and Eguiarte Fruns, newly minted professors at UNAM. They joined, and NASAapproved the 3-year project.

Stromatolites, reeflike colonies of carbonate-secreting cyanobacteria, abounded in Precambrian seasand thrive at Cuatro Cinegas.

With two children in tow, the couple met Minckley and Elser at Cuatro Cinegas. Next to the turquoise-blue waters of La Becerrapoza, Minckley told them he believed the ecosystem was a glimpse of deep time. Do you see these miniature snails in my hand? Souza Saldvar recalls him saying. I just scooped them from the springhead, but their direct ancestors were eating sulfur bacteria in hydrothermal vents 220 million years ago in the bottom of the ancient Pacific.

Based on the water chemistrylow in phosphorus, iron, and nitrogenand the presence of living stromatolites, Minckley believed Cuatro Cinegas re-created the marine conditions found worldwide millions of years ago. He challenged the two researchers to explore its mysteriesand to protect itspozas. Only you, as Mexicans, can save them from the extinction caused by humans, Souza Saldvar recalls him saying.

Minckleydied2 years later, in 2001.

To inventory the full diversityof microbes at Cuatro Cinegas and trace their relationships, Souza Saldvar needed to study their DNA. To do so, scientists normally take microbial samples from a site and grow them in a lab. But many bacteria and archaea are difficult to culture, and only a few groups at the time had successfully analyzed DNA isolated directly from the environment. High magnesium levels in the water and slime from the microbes made isolating DNA from thepozasespecially difficult.

But Souza Saldvar and her students Ana Escalante and Laura Espinosa Asuar made a start. In 2006, they reported in theProceedings of the National Academy of Sciencesthat they had found 38 distinct groups of microbesfour times as many as in a typical salt marshcorresponding to 10 major lineages of bacteria and one of archaea. Half the bacterial groupswere most closely related to marine microbes. Almost 10% of the groups resembled ones that live on hydrothermal ventsfissures deep in the ocean where microbes thrive despite extreme heat and mineral concentrations.

As Minckley had suspected, Cuatro Cinegas had somehow preserved ancient marine life forms deep in the desert, more than 500 kilometers from the Gulf of Mexico, at a site where the last seas retreated some 20 million years ago.

Valeria Souza Saldvar and Luis Eguiarte Fruns (top) have spent 20 years studying biodiversity at Cuatro Cinegas, where they have found thousands of new species in living structures like a bacterial mat (bottom).

The deep time aspect [of Cuatro Cinegas] is very surprising, Travisano says. It is a true lost world, preserved by the hostile water chemistry, he and the Mexican team argued in a 2018 paper ineLife. Millions of years ago, they proposed, ancient marine ancestors found their way to the place,adapted to the extreme environment, and didnt change much.

Thepozasthemselves are not particularly ancient. The springs that nurture them are fed by deep aquifers in Sierra San Marcos y Pinos, filled with water accumulated during the last ice ages, Eguiarte Fruns says. Now, the water seeps to the surface because of an active fault beneath the basin. It rises through ancient marine sediments, picking up its unusual chemistry along the way. Somehow, the ancient microbespersisted and diversifiedin a succession of springs that must have appeared and vanished throughout geologic time. As in an ancient clock, Souza Saldvar says, all the original mechanisms are still working together to sustain unusual life.

To Frederick Cohan, a microbial ecologist at Wesleyan University who is not part of the Cuatro Cinegas project, the fact that many of the microbes are related to marine species and not species found inland is compelling. I think its saying those organisms are anciently there.

When the researcherslooked at the stromatolites, theyfound even more diversity. Samples from one site, Pozas Azules II, yielded more than 58,000 distinct microbial sequences, predominantly from bacterianot a direct count of species, but an indicator of biodiversity. In the Ro Mezquites, a stream that flows through the northern part of the basin and recharges several pools, they identified 30,000 sequences, mostly from cyanobacteria. More than 1000 sequences from Pozas Azules II appeared to be from archaea, the researchers reported inEnvironmental Microbiologyin 2009. The stromatolites also teemed with bacteria-infecting virusesstrains that wereunique to each pooland resembled marine viruses.

Studying the microbes hasnt been easy. There are thousands and thousands of new bacteria that we cant grow in culture, Souza Saldvar says. They could, however, identify some startling adaptations to the extreme conditions. In one bacterium found only in El Churince, a system of lagoons andpozason the western part of the basin, researchers sequenced the smallest genome ever found in its genus,Bacillus. The work, led by Gabriela Olmedo lvarez, a genetic engineer at Center for Research and Advanced Studies of the National Polytechnic Institute, Irapuato, also showed that the microbeB. coahuilensiscould synthesize membrane sulfolipids. This meant that, like some plants and cyanobacteria, it could use sulfur from the environmentinstead of phosphorusto form its cell membranes.

Shallow, mineral-rich pools and lagoons, with conditions like those in ancient oceans, are hot spots of microbial diversity. Floating mats at Cuatro Cinegas teem with the primordial microbes known as archaea, leading researchers to call them archaean domes.

(GRAPHIC) N. DESAI/SCIENCE; (DATA) GARCIA-MALDONADO ET AL., EXTREMOPHILES, DOI 10.1007/S00792-018-1047-2; CENTENO ET AL., MICOBIOLOY ECOLOGY, DOI: 10.1111/J.1574-6941.2012.01447

It likely stole these genes from a cyanobacterium, Olmedo lvarez says, enabling it to cope with scarce phosphorus, a condition thought to have prevailed in Earths earliest oceans. The microbes small genome may also have helped it thrive, as it required less phosphorus to build its DNA. Olmedo lvarez thinks the organism may offer a glimpse of the stratagems used by early microbes to adapt to their new environment.

Were just starting to understand the depth of diversity, says Olmedo lvarez, who found thatB. coahuilensisis itself starting tosplit into strainswith variations in phosphorus metabolism.

The low phosphorus conditions found in Cuatro Cinegas not only promoted local adaptations, but alsoaccelerated microbial diversification, Souza Saldvar and Elser argued in a perspective published in 2008 inNature Reviews Microbiology. Bacteria normally share bits of DNA with their neighbors in a process called horizontal gene transfer, which blurs the divisions between strains. But in Cuatro Cinegas, the microbeshungry for phosphorusessentially consume free DNA rather than incorporating it into their genomes. They will eat the DNA to get the phosphorus, Elser says.

Besides offering insights into evolution, Cuatro Cinegass microbial diversity may hold practical payoffs. Cuatro Cinegas is one of the richest places on the planet for genetic resources, Souza Saldvar says. For example, most modern antibiotics are derived from actinobacteria, which are abundant in thepozas. Susana De la Torre Zavala, a biotechnologist at the Autonomous University of Nuevo Len (UANL), University City, is searching for potential antibiotics in a library of 350 actinobacteria from the basin. Her team has also found that an extract from a microalga living in the poolsshows anticancer activity.

Agriculture, too, could benefit, Olmedo lvarez says. By 2050, the reservoirs of phosphorus that help sustain global harvests could become scarce, and the microbesability to concentrate the element from different sourcescould hold solutions. Were understanding Cuatro Cinegas, but were also understanding basic principles of ecological interactions that have an application in medicine and agriculture, she says.

As the scientific storyof Cuatro Cinegas unfolded, its fate has hung in the balance, with Souza Saldvar fighting a long series of battles over its water with local farmers and landowners, dairy companies, and politicians. Her weapons have been her rising scientific profile and a tireless outreach to the public, especially young people.

Souza Saldvar has drawn fireduring a 2013 microbiology congress, police had to protect her from protesting localsbut she has won a series of victories. In 2007, the daughter of the CEO of LALA, a giant dairy consortium with roots in the state of Coahuila, told her father she wouldnt speak to him because he was killing Cuatro Cinegas, Souza Saldvar says. The executive promptly scheduled a meeting with the scientist. You need to change your cows diet, Souza Saldvar says she told him, refusing to accept a courtesy yogurt he offered. Ill accept your yogurt when you do so. He promised not only to stop buying the regions alfalfa, but also to invest in environmental education projects for local children.

Two years later, she won an unusual ally, the powerful Mexican billionaire Carlos Slim. His foundation collaborated with the World Wildlife Fund (WWF) to buy the land surrounding El Churince in the western basin, and to provide researchers with a 5-year, 18 million Mexican peso ($1.4 million) grant to study Souza Saldvars favoritepoza. This allowed them to set up the infrastructure to perform long-term experiments. But it did not save the water.

Endemic fishes and turtles first drew scientists to Cuatro Cinegas, where they stumbled on its less visible microbial riches.

In 2010, Mexicos National Water Commission (CONAGUA) set out to replace the open, leaky canals, which lose 75% of the drained water, with less wasteful enclosed conduits. But the project was abandoned midwaymost likely because of corruptionand the old canals were never closed. As Cuatro Cinegas continued to dry up, the researchers raced to study El Churince, finding 5167 distinct species of bacteria and archaea in the last remaining pool. A close inspection of the genomes ofBacillusbacteria from one single square kilometer increased the known diversity of the group by more than 20%. By comparing DNA sequences, the team traced theBacillusdiversity to two ancient ancestors, one dating back 680 million years, the other 160 million years. Those dates coincide with the breakup of the supercontinents Rodinia and Pangaea, respectively, and the team thinks theoceans that formed during those convulsions carried the ancestral microbesto what is now the Cuatro Cinegas Basin, where they have persisted ever since.

Cohan says thats plausible.Bacillusfrom elsewhere fail to thrive in Cuatro Cinegas, most likely because they are outcompeted by the local microbes and cant adapt to the extreme conditions. And theBacillusspecies from Cuatro Cinegas are not found anywhere else in the world. Its just bizarre, Cohan says, but it makes thepozasso much more valuable and worth saving. Its kind of a paleontological microbial park.

In 2016, El Churince dried up just after the funding from the WWFCarlos Slim Foundation ended. The researchers felt devastated. Souza Saldvar says it was painful to see turtle shells lying on the now-barren soil. Its really sad, Olmedo lvarez says. Its gone.

On the eastern sideof the basin, things are looking brighter. In 2000, the conservation nongovernmental organization Pronatura Noreste acquired the Pozas Azules ranch: 2721 hectares hosting about 100pozas. Pronatura eventually gained rights to the water as well, enabling it to close canals draining thepozasin the ranch. Farmers are now encouraged to adopt water-sparing drip irrigation, and some are growing nopalan edible cactus popular in Mexican cuisinewhich requires much less water than alfalfa.

The researchers have focused their recent studies on Pozas Azules. In 2019, after an unusual spring rain, the team noticed alien-looking structures in the shallow waters of a site near Pozas Azules II: white microbial mats buoyed by gas. The gas appeared to be largely methane, and a genetic analysis showed the mats were teeming with archaea230 distinct species,they report in a preprint. That makes the spot the most diverse place of archaea that we know of, De la Torre Zavala says.

Now, the team hopes to analyze samples from the structures, which it calls archaean domes, in search of the elusive Asgard archaea, organisms previously found only in the deep ocean and thought tohold clues to the evolution of simple microbesinto complex eukaryotes. Although some in her team are skeptical, Souza Saldvar is convinced they will find them. Valerias usually right, De la Torre Zavala says.

Shaped and seeded with life by ancient seas, the Cuatro Cinegas Basin lies at the foot of the distant Sierra San Marcos. The white dunes bordering the basin are made of gypsum, a legacy of a Jurassic ocean.

Such prospects have added to Souza Saldvars determination to preserve Cuatro Cinegas, and she is enlisting young people for support. In every field trip since 2004, her team has spent time with students from the local high school, showing them how to use a microscope and take simple environmental measurements, and teaching them about sustainable agriculture. In 2011, with funding from the LALA Foundation and the WWFCarlos Slim Foundation, the scientists set up a college-level molecular biology lab at the school, which is now ranked among the best rural high schools in Mexico.

Hctor Arocha Garza is one of its graduates. Inspired by the secrets of Cuatro Cinegas, he pursued a Ph.D. in biotechnology at UANL with De la Torre Zavala, then returned to his hometown. My heart was in Cuatro Cinegas, he says. Now, hes leading the scientific branch of a privately fundedmegaproject called Cuatro Cinegas 2040that aims to build a science museum and make Cuatro Cinegas a scientific tourism destination, while supporting education and medical care for the villages young people.

The effort comes at a critical moment. More than 90% of the marshes are gone, and somepozasand lagoons are dry. But this year, CONAGUA committed toregulating water usageand closing illegal wells, and Pronatura Noreste will close the Saca Salada Canal, which drains the Ro Mezquites, as soon as the COVID-19 pandemic permits.

Those developments, and stories like Arocha Garzas, give Souza Saldvar hope for the future of Cuatro Cinegas. It has been a very complicated, long, and difficult process, she says. But now, she wrote in a recent book, There is a revolution occurring in this oasis: Science is the tool and kids are the drivers.

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Pools in the Mexican desert are a window into Earth's early life - Science Magazine

A team led by Case Western Reserve University medical researchers has developed a potential treatment method for Pelizaeus-Merzbacher disease (PMD), a fatal neurological disorder that produces severe movement, motor and cognitive dysfunction in children. It results from genetic mutations that prevent the body from properly making myelin, the protective insulation around nerve cells.

Paul Tesar, professor of genetics and genome sciences, School of Medicine

Using mouse models, the researchers identified and validated a new treatment target-a toxic protein resulting from the genetic mutation. Next, they successfully used a family of drugs known as ASOs (antisense oligonucleotides) to target the ribonucleic acid (RNA) strands that created the abnormal protein to stop its production. This treatment reduced PMDs hallmark symptoms and extended lifespan, establishing the clinical potential of this approach.

By demonstrating effective delivery of the ASOs to myelin-producing cells in the nervous system, researchers raised the prospect for using this method to treat other myelin disorders that result from dysfunction within these cells, including multiple sclerosis (MS).

Their research was published online July 1 in the journal Nature.

The pre-clinical results were profound. PMD mouse models that typically die within a few weeks of birth were able to live a full lifespan after treatment, said Paul Tesar, principal investigator on the research, a professor in the Department of Genetics and Genome Sciences at the School of Medicine and the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics. Our results open the door for the development of the first treatment for PMD as well as a new therapeutic approach for other myelin disorders.

Study co-authors include an interdisciplinary team of researchers from the medical school, Ionis Pharmaceuticals Inc., a Carlsbad, California-based pioneer developer of RNA-targeted therapies, and Cleveland Clinic. First author Matthew Elitt worked in Tesars lab as a Case Western Reserve medical and graduate student.

PMD is a rare, genetic condition involving the brain and spinal cord that primarily affects boys. Symptoms can appear in early infancy and begin with jerky eye movements and abnormal head movements. Over time, children develop severe muscle weakness and stiffness, cognitive dysfunction, difficulty walking and fail to reach developmental milestones such as speaking. The disease cuts short life-expectancy, and people with the most severe cases die in childhood.

The disease results from errors in a gene called proteolipid protein 1 (PLP1). Normally, this gene produces proteolipid protein (PLP) a major component of myelin, which wraps and insulates nerve fibers to allow proper transmission of electrical signals in the nervous system. But a faulty PLP1 gene produces toxic proteins that kill myelin producing cells and prevent myelin from developing and functioning properly-resulting in the severe neurological dysfunction in PMD patients.

PMD impacts a few thousand people around the world. So far, no therapy has lessened symptoms or extended lifespans.

For nearly a decade, Tesar and his team have worked to better understand and develop new therapies for myelin disorders. They have had a series of successes, and their myelin-regenerating drugs for MS are now in commercial development.

In the current laboratory work, the researchers found that suppressing mutant PLP1 and its toxic protein restored myelin-producing cells, produced functioning myelin, reduced disease symptoms and extended lifespans.

After validating that PLP1 was their therapeutic target, the researchers pursued pre-clinical treatment options. They knew mutations in the PLP1 gene produced faulty RNA strands that, in turn, created the toxic PLP protein.

Additional team members included Lilianne Barbar, Elizabeth Shick, Yuka Maeno-Hikichi, Mayur Madhavan, Kevin Allan, Baraa Nawash, Artur Gevorgyan, Stevephen Hung, Zachary Nevin, Hannah Olsen, Daniela Schlatzer, David LePage, Weihong Jiang and Ronald Conlon from Case Western Reserve University School of Medicine; Berit Powers, Hien Zhao, Adam Swayze and Frank Rigo from Ionis Pharmaceuticals; and Midori Hitomi from Cleveland Clinic.

This research was supported by grants from the National Institutes of Health, New York Stem Cell Foundation and European Leukodystrophy Association. Philanthropic support was provided by the Geller, Goodman, Fakhouri, Long, Matreyak, Peterson and Weidenthal families and the CWRU Research Institute for Childrens Health.

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Case Western Reserve University-led team develops new approach to treat certain neurological diseases - Mirage News

For years Ive walked a tightrope with my professional life on one side and personal life on the other. Two very separate existences. Slowly, as Ive become more comfortable sharing my personal story the tightrope has become steadier. I have become more comfortable with the rope and learnt to stop looking down.

Today, after years of balancing (well at least attempting to), the tightrope has disintegrated, and Im still standing, now ready to share my story.

I have been dancing on the personal-work-life tightrope since 2012. The journey began eight years ago when my second daughter was three months old and I started consulting to AIA Australia to help launch Vitality into the Australian market.

Over the next three years, I juggled the darkest times of my personal life while effectively working in a start-up. I was in survival mode, emotionally for myself and literally for my children and I rarely mentioned a word of it to my colleagues.

My husband and I were dealing with our 2.5 year-old, Jaeli, who had developed uncontrolled seizures (in fact hundreds a day), extreme behaviours, autistic features, childhood insomnia, three-hour nightly and daily screaming fits, self-injurious behaviour and cognitive delays.

My second daughter, Dali, born 2 years after Jaeli, had hit all of her milestones at the age of one, beforewe saw it that first sign the subtle eye lid seizures. This time we knew how those subtle eyelid seizures would progress.

We were heartbroken.

In those early years, we were driven by the sense of urgency to get a diagnosis and fix our kids, acutely aware of the neurodevelopmental plasticity window closing further every day.

My survival technique was to compartmentalise.

I was in survival mode at home and work was my escape. An escape from the helplessness I felt watching our beautiful girls suffer, every attempt to help them only making them worse.

I didnt intentionally hide the situation from my colleagues, but I rarely mentioned it. I didnt want to burden others with my pain, I didnt want them to pity me and I definitely didnt want to be treated differently.

Unknowingly, I was protecting my illusion of control.

Our journey took a new direction and energy when we finally received a diagnosis for the girls in 2016. At that time they were four and six years old. We were one of the first in Australia to undergo whole genome sequencing, and after five long years we had a name for our enemy. It was a rare genetic epilepsy called Syngap. At the time, there were less than 100 diagnosed in the world, now, four years later, there are almost 600.

Knowledge is power and armed with a diagnosis, we became empowered to change our daughters destinies. We were buoyed learning that there has never been a better time for science, medical discoveries, precision medicine and gene therapy.

We connected with other families, with researchers and clinicians who gave us hope that precision medicine was a realistic concept for our kids.

Next, we established Syngap Research Fund Australia, co-founded Genetic Epilepsy Team Australia (GETA) and the Syngap Global Network. We advocated for whole genome sequencing, jumped into collating data on the condition which inspired the largest Syngap study, published in the neurology journal in 2019 on which I was a co-author. We lobbied government, leading to a $2m investment in genetic epilepsy research, which kickstarted our Syngap research project in 2018 at the Florey Institute for Neuroscience and Mental Health.

Weve learnt along the way that those who bear the burden of disease have an unrelenting passion like no other which accelerates scientific breakthroughs.

And, Ive slowly learnt, that the two worlds professional and personal that I had deliberately kept apart, could in fact benefit one another. I learnt the tightrope could in fact become a runway.

Professionally, I thrive in a team environment, partly because I own my shortcomings and naturally seek partnerships that combine complementary skillsets and genuinely subscribe to the shared value concept. I like to rely on others and I like to be relied on.

Personally, I am inspired by those I fight shoulder to shoulder with in battle from our Genetic Epilepsy Team Australia group, to the Syngap Global Network team, and my husband who is so driven and optimistic, grateful for that optimism especially when I am not.

Only recently have I realised the same theory of combining complementary skills applies to the two versions of myself the professional version and the rare disease mum version that each contribute to the same person.

Im surprised and grateful that the skills Ive obtained in each of these versions of myself are transferrable. That my persistence, optimism, passion, empathy, tolerance and resilience straddle both sides of that tightrope, ultimately bringing strength and balance to both.

Through this journey, Ive also learnt the power of gratitude. I am grateful for my family, friends, community and personal network that have loved me in my darkest times. And, I am indebted to AIA Australia, and particularly Damien Mu, who have supported me professionally, and who chose to keep my tightrope taut when I felt the need to keep my two roles as employee and rare disease mum balanced, but apart.

Today, after eight years trying to balance the tightrope, I feel empowered by that runway on which I can make a difference in both my professional and personal roles.

This is an edited version of a post that Danielle first published on LinkedIn. Its shared here with permission.

For more information on Syngap Research Australia, click here. Or check them out on Facebook or Twitter.

You can find more information on GETA: Genetic Epilepsy Team Australia here, or on Facebook or Twitter

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I've been walking a work-life tightrope. It's finally disintegrated and I'm ready to share my story - Women's Agenda

Snoqualmie, WA, July 03, 2020 --(PR.com)-- Gene C. Rousseau of Snoqualmie, Washington has been recognized as a Professional of the Year for 2020 by Strathmores Whos Who Worldwide Edition for his outstanding achievements and contributions for over 41 years in the machinery field.

About Gene C. RousseauGene C. Rousseau is the owner of TNG Machinery LLC, a longtime salesman for multiple woodworking companies covering Washington State and the Panhandle of Idaho who offers integrated metric solutions for wood, plastics and stone. TNG Machinery provides services to one man shops as well as large corporations. Their technology solutions can increase production and improve bottom lines. With over 41 years experience, Mr. Rousseau offers multiple values and liaises with cabinet companies. He provides metric solutions and assists with metric evaluations. Mr. Rousseau also serves as an intermediary for buying and selling used and new equipment.

Born on May 14, 1957 in Seattle, Washington, Gene attended Highline Community College and the University of Washington. Throughout his career, Mr. Rousseau has sold to the wood, plastic, stone and aerospace industries and has driven over 4.5 million miles. He was awarded Dealer of the Year in 2006 and 2007.

Gene married his beautiful wife Nicole in 1997 and they have two children, Tanner and Sydney. In his spare time, he enjoys fishing and coaching football.

For further information, contact https://www.tngmachinery.com.

About Strathmores Whos Who WorldwideStrathmores Whos Who Worldwide highlights the professional lives of individuals from every significant field or industry including business, medicine, law, education, art, government and entertainment. Strathmores Whos Who Worldwide is both an online and hard cover publication where we provide our members current and pertinent business information. It is also a biographical information source for thousands of researchers, journalists, librarians and executive search firms throughout the world. Our goal is to ensure that our members receive all of the networking, exposure and recognition capabilities to potentially increase their business.

Contact Information:Strathmore WorldwideSusan Perrault516-677-9696Contact via Emailwww.strathmoreworldwide.comSyndi Reibman

Read the full story here: https://www.pr.com/press-release/815106

Press Release Distributed by PR.com

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Gene C. Rousseau Recognized as a Professional of the Year for 2020 by Strathmore's Who's Who Worldwide - Benzinga

Newswise Massachusetts Eye and Ear, a member hospital of Mass General Brigham, is entering into an exclusive licensing agreement with Biogen to develop a potential treatment for inherited retinal degeneration due to mutations in the PRPF31 gene, which are among the most common causes for autosomal dominant retinitis pigmentosa.

Inherited retinal degenerations (IRDs), such as retinitis pigmentosa, are a group of blinding eye diseases caused by mutations in over 270 different genes. Mutations in the PRPF31 gene are the second most common cause of dominant IRD and lead to defects in the function of the retinal pigment epithelial (RPE) cells and photoreceptors of the retina. Previous lab-based research performed by members of the Ocular Genomics Institute at Harvard Ophthalmology, led by Eric A. Pierce, MD, PhD, demonstrated that adeno-associated virus (AAV)-mediated gene augmentation therapy for PRPF31 can restore normal function to PRPF31 mutant RPE cells.

Biogen (Nasdaq: BIIB), a biopharmaceutical company that discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological and neurodegenerative diseases as well as related therapeutic adjacencies, will build upon this prior work, and conduct the studies needed for clinical development of PRPF31 gene therapy. This includes the pre-clinical studies needed to support progression to clinical trials of PRPF31 gene therapy. As part of the agreement, Biogen will receive an exclusive license to develop the product worldwide and will be responsible for all U.S. Food and Drug-Administration (FDA) required investigational new drug (IND) enabling studies, clinical development and commercialization.

The treatment of IRDs with highly effective AAV-based gene therapies is core to Biogens ophthalmology strategy, said Chris Henderson, Head of Research, Biogen. This agreement underscores our commitment to that strategy and builds off of our acquisition of Nightstar Therapeutics in 2019 and our active clinical trials of gene therapies for different genetic forms of IRD. We are excited to work with Massachusetts Eye and Ear and look forward to applying our preclinical and clinical experience to their leading PRPF31 program.

We are thrilled to work with Biogen, who will bring to this effort its deep experience with the clinical development process, as we work toward our goal of developing a gene therapy for people with PRPF31-related eye disease, added Dr. Pierce, who is the William F. Chatlos Professor of Ophthalmology at Harvard Medical School. My ultimate hope for patients with inherited retinal disorders due to mutations in PRPF31 is that a gene therapy will preserve and potentially restore some of their vision.

About the Ocular Genomics Institute

The Ocular Genomics Institute at Harvard Ophthalmology aims to translate genomic medicine into precision ophthalmic care for patients with inherited eye disorders. It is home to one of the leading centers for early-phase clinical trials of therapies for inherited retinal degenerations, with seven gene-based and one stem cell trial currently in progress. The group works in conjunction with other departments throughout Harvard Medical School and Mass. Eye and Ear, including the Bioinformatics Center and Grousbeck Gene Therapy Center.

Dr. Pierces lab, established in 2011, is dedicated to research in an effort to improve the understanding of the molecular bases of IRDs so that rational therapies can be developed for these diseases.

In 2018, Mass. Eye and Ear surgeons performed the first post-FDA approval gene therapy for patients with a form of inherited retinal blindness caused by mutations in the gene RPE65 by injecting an AAV-based drug treatment into a patients eye, which restored vision in a 13-year-old boy. This therapy, called Luxturna, is now being used to treat patients with RPE65-associated retinal degeneration around the world.

One of the exciting aspects of our collaboration with Biogen is that mutations in the PRPF31 gene affect approximately 10 to 20 times more people than mutations in the RPE65 gene, said Dr. Pierce. Success with PRPF31 gene therapy could provide visual benefit to more patients, which is our ultimate goal.

Mass. Eye and Ear was one of the first centers to offer life-changing gene therapies to patients with inherited retinal disease, and we are thrilled with this new opportunity to develop a translational retinal therapy that could help even more patients, said Joan W. Miller, MD, Chief of Ophthalmology at Mass. Eye and Ear, Massachusetts General Hospital, and Brigham and Womens Hospital, and Chair of Ophthalmology and the David Glendenning Cogan Professor of Ophthalmology at Harvard Medical School.

According to Chris Coburn, Chief Innovation Officer, Mass General Brigham, the collaboration with Biogen illustrates the importance of academia and industry teaming to solve problems for patients worldwide. We are eager to see this progress reach patients who are challenged by blinding, degenerative eye disease, said Coburn. We look forward to working with Biogen to advance this break-through innovation.

Patients with an inherited retinal disease require genetic testing prior to being considered for any gene therapy treatment.

About Massachusetts Eye and Ear

Massachusetts Eye and Ear, founded in 1824, is an international center for treatment and research and a teaching hospital of Harvard Medical School. A member of Mass General Brigham, Mass. Eye and Ear specializes in ophthalmology (eye care) and otolaryngologyhead and neck surgery (ear, nose and throat care). Mass. Eye and Ear clinicians provide care ranging from the routine to the very complex. Also home to the world's largest community of hearing and vision researchers, Mass. Eye and Ear scientists are driven by a mission to discover the basic biology underlying conditions affecting the eyes, ears, nose, throat, head and neck and to develop new treatments and cures. In the 20192020 Best Hospitals Survey,U.S. News & World Reportranked Mass. Eye and Ear #4 in the nation for eye care and #2 for ear, nose and throat care.For more information about life-changing care and research at Mass. Eye and Ear, visit our blog,Focus, and follow us onInstagram,TwitterandFacebook.

About Harvard Medical School Department of Ophthalmology

The Harvard Medical SchoolDepartment of Ophthalmologyis one of the leading and largest academic departments of ophthalmology in the nation. Composed of nine affiliates (Massachusetts Eye and Ear, which is home to Schepens Eye Research Institute; Massachusetts General Hospital; Brigham and Womens Hospital; Boston Childrens Hospital; Beth Israel Deaconess Medical Center; Joslin Diabetes Center/Beetham Eye Institute; Veterans Affairs Boston Healthcare System; Veterans Affairs Maine Healthcare System; and Cambridge Health Alliance) and several international partners, the department draws upon the resources of a global team to pursue a singular goaleradicate blinding diseases so that all children born today will see throughout their lifetimes. Formally established in 1871, the department is committed to its three-fold mission of providing premier clinical care, conducting transformational research, and providing world-class training for tomorrows leaders in ophthalmology.

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Massachusetts Eye and Ear Enters Licensing Agreement with Biogen to Develop Treatment for Inherited Retinal Disorder - Newswise

TOKYO, July 1, 2020 /PRNewswire/ --Hitachi, Ltd.(TSE: 6501, "Hitachi") and ThinkCyte, Inc. ("ThinkCyte") today announced that they have entered into a collaboration focused on developing an artificial intelligence (AI)-driven cell analysis and sorting system. Hitachi provides a broad range of solutions such as automated cell culture technologies to pharmaceutical companies in the value chain*1 of the regenerative medicine and cell therapy industry. Through the addition of this cell analysis and sorting system to the value chain, Hitachi continues contributing to cost reductions in the manufacturing of regenerative medicine and cell therapy products.Further, Hitachi and ThinkCyte are promoting collaboration with pharmaceutical companies and research institutes working in the field of regenerative medicine and cell therapy to expedite the development of the system toward commercialization.

The practical applications of regenerative medicine and cell therapy using cells for treatment have been expanding rapidly with the first regulatory approval of CAR-T*2 therapy for leukemia in 2017 in the United States and 2019 in Japan. The global market for regenerative medicine and cell therapy is expected to grow from US$ 5.9 billion (JPY 630 billion) in 2020 to US$ 35.4 billion (JPY 3.8 trillion) in 2025*3. In order to scale up treatment using regenerative medicine and cell therapy products, it is critical to ensure consistent selection and stable supply of high quality cells in large quantities and at a low costs.

Hitachi has been providing large-scale automated induced pluripotent stem (iPS) cell culture equipment, cell processing facilities (CPFs), manufacturing execution systems(MES), and biosafety cabinets among other products to pharmaceutical companies and research institutes, and has developed a value chain to meet a variety of customer needs in the regenerative medicine and cell therapy industry. Hitachi has also been carrying out collaborative research projects with universities, research institutes, and other companies to develop core technologies for pharmaceutical manufacturing instruments and in vitro diagnostic medical devices, prototyping for mass production, and working on manufacturing cost reduction and the development of stable and reliable instruments.

ThinkCyte has been performing research and development focused on high-throughput single cell analysis and sorting technology to precisely analyze and isolate target cells. While such single cell analysis and sorting technologies are vital to life science and medical research, it has been thought impossible to achieve high-throughput cell sorting based on high-content image information of every single cell. ThinkCyte has developed the world's first Ghost Cytometrytechnology to achieve high-throughput and high-content single cell sorting*4and has been conducting collaborative research projects with multiple pharmaceutical companies and research institutes to utilize this technology in life science and medical fields.

Hitachi and ThinkCyte have initiated a joint development of the AI-driven cell analysis and sorting system based on their respective technologies, expertise, and know-how. By combining ThinkCyte's high-throughput and high-content label-free single cell sorting technology and Hitachi's know-how and capability to producing stably operative instruments on a large scale, the two companies will together develop a novel reliable system to enable high-speed label-free cell isolation with high accuracy, which has been difficult to achieve with the existing cell sorting techniques, and to realize stable, low-cost and large-scale production of cells for regenerative medicine and cell therapy.

Hitachi and ThinkCyte will further advance partnerships with pharmaceutical companies and research institutes that have been developing and manufacturing regenerative medicines and cell therapy products in Japan and other countries where demand is expected to be significant, such as North America, in order to make this technology a platform for the production of regenerative medicines and cell therapy products. At the same time, taking advantage of the high-speed digital processing technologies cultivated through the development of information and communication technology by the Hitachi group, Hitachi will integrate this safe and highly reliable instrument in its value chain for regenerative medicine and contribute to the growth of the regenerative medicine and cell therapy industry.

Note:

*1. Cell manufacturing processes, including cultivation, selection, modification, preservation, product quality control, etc.

*2. Chimeric Antigen Receptor T cells that have been genetically engineered to produce an artificial T-cell receptor for use in immunotherapy.

*3. Division of Regenerative Medicine, Japan Agency for Medical Research and Development, The final report for market research on regenerative medicine and gene therapy (2020).

*4. S, Ota et al., Ghost Cytometry, Science, 360, 1246-1251 (2018).

About the AI-driven cell analysis and cell sorting technologyThinkCyte has developed high-throughput image-based cell sorting technology based on the Ghost Cytometry technology by integrating the principles of advanced imaging technology, machine learning, and microfluidics. By applying structured illumination to cell imaging, structural information of a single cell can be converted to one-dimensional waveforms for high-throughput data analysis. Based on the judgment of a machine-learning (AI) model developed using the waveform data, target cells are isolated in a microfluidic device with high throughput and with minimal damage to the cells.

This data analysis approach eliminates time-consuming image reconstruction processes and allows high-throughput image-based single cell sorting, enabling the discrimination of cells that were previously considered difficult to distinguish by the human eye. Conventional cell sorting methods rely on the use of labels such as cell surface markers for cell sorting; in contrast, ThinkCyte's technology can sort cells without such labels by employing this unique approach. In addition to the field of regenerative medicine and cell therapy, this technology can also revolutionize drug discovery and in vitrodiagnostics fields.

About Hitachi, Ltd.Hitachi, Ltd. (TSE: 6501), headquartered in Tokyo, Japan, is focused on its Social Innovation Business that combines information technology (IT), operational technology (OT) and products. The company's consolidated revenues for fiscal year 2019 (ended March 31, 2020) totaled 8,767.2 billion yen ($80.4 billion), and it employed approximately 301,000 people worldwide. Hitachi drives digital innovation across five sectors - Mobility, Smart Life, Industry, Energy and IT - through Lumada, Hitachi's advanced digital solutions, services, and technologies for turning data into insights to drive digital innovation. Its purpose is to deliver solutions that increase social, environmental and economic value for its customers. For more information on Hitachi, please visit the company's website at https://www.hitachi.com.

About ThinkCyte, Inc.ThinkCyte, headquartered in Tokyo, Japan, is a biotechnology company, which developsinnovative life science research, diagnostics,and treatmentsusingintegrated multidisciplinary technologies, founded in 2016. The company focuses on the research and development of drug discovery, cell therapy, and diagnostic platforms using its proprietary image-based high-throughput cell sorting technology In June 2019, the company was selected for J-Startup by the Ministry of Economy, Trade and Industry of Japan. For more information on ThinkCyte, please visit the company's website at https://thinkcyte.com.

ContactsHitachi, Ltd.Analytical Systems Division, Healthcare Division, Smart Life Business Management Divisionhttps://www8.hitachi.co.jp/inquiry/healthcare/en/general/form.jsp

ThinkCyte, Inc.https://thinkcyte.com/contact

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Hitachi and ThinkCyte announce collaboration to develop an AI-driven cell analysis and sorting system - BioSpace