Tag Archives: autism

Café Scientifique Vancouver (Canada) talk on July 31st. 2018: Test Tubes to Teaching: How Anti-Vaxxers and a Global Financial Crisis Shaped my Career

I received (via email) this Café Scientifique July 15, 2018 notice ,

Our next café will happen on TUESDAY, JULY 31ST at 7:30PM in the back
room at YAGGER’S DOWNTOWN (433 W Pender). Our speaker for the
evening will be DR. NIENKE VAN HOUTEN from THE FACULTY OF HEALTH
SCIENCES AT SFU. Her topic will be:

TEST TUBES TO TEACHING: HOW ANTI-VAXXERS AND A GLOBAL FINANCIAL CRISIS
SHAPED MY CAREER

Part research talk, and part memoir, Dr. van Houten will describe her
career progression from vaccine design scientist to education
researcher. From early childhood, Dr. van Houten developed an
unrelenting interest in human biology and infectious diseases and made
it her goal to become a scientist. Her passion for vaccines came about,
in part, due to the publicity surrounding the infamous retracted paper
in _The Lancet_ that erroneously connected measles vaccination with
autism. Her Ph.D. and postdoctoral research focused on how vaccines
work, and she engineered anti-viral vaccines to produce focused antibody
responses. However, her plan of working in the pharmaceutical industry
was sidelined by the financial crash of 2008, and she was offered a full
time teaching faculty position. This created an opportunity to study how
students think critically about science and apply those findings to
train students to recognize bad science such as that promoted by
anti-vaxxers and other garbage “science” that pervades our society.

We hope to see you there!

I wasn’t able to find out much more about Dr. van Houten and her work but her SFU profile page is here.

Yes! Art, genetic modifications, gene editing, and xenotransplantation at the Vancouver Biennale (Canada)

Patricia Piccinini’s Curious Imaginings Courtesy: Vancouver Biennale [downloaded from http://dailyhive.com/vancouver/vancouver-biennale-unsual-public-art-2018/]

Up to this point, I’ve been a little jealous of the Art/Sci Salon’s (Toronto, Canada) January 2018 workshops for artists and discussions about CRISPR ((clustered regularly interspaced short palindromic repeats))/Cas9 and its social implications. (See my January 10, 2018 posting for more about the events.) Now, it seems Vancouver may be in line for its ‘own’ discussion about CRISPR and the implications of gene editing. The image you saw (above) represents one of the installations being hosted by the 2018 – 2020 edition of the Vancouver Biennale.

While this posting is mostly about the Biennale and Piccinini’s work, there is a ‘science’ subsection featuring the science of CRISPR and xenotransplantation. Getting back to the Biennale and Piccinini: A major public art event since 1988, the Vancouver Biennale has hosted over 91 outdoor sculptures and new media works by more than 78 participating artists from over 25 countries and from 4 continents.

Quickie description of the 2018 – 2020 Vancouver Biennale

The latest edition of the Vancouver Biennale was featured in a June 6, 2018 news item on the Daily Hive (Vancouver),

The Vancouver Biennale will be bringing new —and unusual— works of public art to the city beginning this June.

The theme for this season’s Vancouver Biennale exhibition is “re-IMAGE-n” and it kicks off on June 20 [2018] in Vanier Park with Saudi artist Ajlan Gharem’s Paradise Has Many Gates.

Gharem’s architectural chain-link sculpture resembles a traditional mosque, the piece is meant to challenge the notions of religious orthodoxy and encourages individuals to image a space free of Islamophobia.

Melbourne artist Patricia Piccinini’s Curious Imaginings is expected to be one of the most talked about installations of the exhibit. Her style of “oddly captivating, somewhat grotesque, human-animal hybrid creature” is meant to be shocking and thought-provoking.

Piccinini’s interactive [emphasis mine] experience will “challenge us to explore the social impacts of emerging biotechnology and our ethical limits in an age where genetic engineering and digital technologies are already pushing the boundaries of humanity.”

Piccinini’s work will be displayed in the 105-year-old Patricia Hotel in Vancouver’s Strathcona neighbourhood. The 90-day ticketed exhibition [emphasis mine] is scheduled to open this September [2018].

Given that this blog is focused on nanotechnology and other emerging technologies such as CRISPR, I’m focusing on Piccinini’s work and its art/science or sci-art status. This image from the GOMA Gallery where Piccinini’s ‘Curious Affection‘ installation is being shown from March 24 – Aug. 5, 2018 in Brisbane, Queensland, Australia may give you some sense of what one of her installations is like,

Courtesy: Queensland Art Gallery | Gallery of Modern Art (QAGOMA)

I spoke with Serena at the Vancouver Biennale office and asked about the ‘interactive’ aspect of Piccinini’s installation. She suggested the term ‘immersive’ as an alternative. In other words, you won’t be playing with the sculptures or pressing buttons and interacting with computer screens or robots. She also noted that the ticket prices have not been set yet and they are currently developing events focused on the issues raised by the installation. She knew that 2018 is the 200th anniversary of the publication of Mary Shelley’s Frankenstein but I’m not sure how the Biennale folks plan (or don’t plan)  to integrate any recognition of the novle’s impact on the discussions about ‘new’ technologies .They expect Piccinini will visit Vancouver. (Note 1: Piccinini’s work can  also be seen in a group exhibition titled: Frankenstein’s Birthday Party at the Hosfselt Gallery in San Francisco (California, US) from June 23 – August 11, 2018.  Note 2: I featured a number of international events commemorating the 200th anniversary of the publication of Mary Shelley’s novel, Frankenstein, in my Feb. 26, 2018 posting. Note 3: The term ‘Frankenfoods’ helped to shape the discussion of genetically modified organisms and food supply on this planet. It was a wildly successful campaign for activists affecting legislation in some areas of research. Scientists have not been as enthusiastic about the effects. My January 15, 2009 posting briefly traces a history of the term.)

The 2018 – 2020 Vancouver Biennale and science

A June 7, 2018 Vancouver Biennale news release provides more detail about the current series of exhibitions,

The Biennale is also committed to presenting artwork at the cutting edge of discussion and in keeping with the STEAM (science, technology, engineering, arts, math[ematics]) approach to integrating the arts and sciences. In August [2018], Colombian/American visual artist Jessica Angel will present her monumental installation Dogethereum Bridge at Hinge Park in Olympic Village. Inspired by blockchain technology, the artwork’s design was created through the integration of scientific algorithms, new developments in technology, and the arts. This installation, which will serve as an immersive space and collaborative hub for artists and technologists, will host a series of activations with blockchain as the inspirational jumping-off point.

In what is expected to become one of North America’s most talked-about exhibitions of the year, Melbourne artist Patricia Piccinini’s Curious Imaginings will see the intersection of art, science, and ethics. For the first time in the Biennale’s fifteen years of creating transformative experiences, and in keeping with the 2018-2020 theme of “re-IMAGE-n,” the Biennale will explore art in unexpected places by exhibiting in unconventional interior spaces.  The hyperrealist “world of oddly captivating, somewhat grotesque, human-animal hybrid creatures” will be the artist’s first exhibit in a non-museum setting, transforming a wing of the 105-year-old Patricia Hotel. Situated in Vancouver’s oldest neighbourbood of Strathcona, Piccinini’s interactive experience will “challenge us to explore the social impacts of emerging bio-technology and our ethical limits in an age where genetic engineering and digital technologies are already pushing the boundaries of humanity.” In this intimate hotel setting located in a neighborhood continually undergoing its own change, Curious Imaginings will empower visitors to personally consider questions posed by the exhibition, including the promises and consequences of genetic research and human interference. …

There are other pieces being presented at the Biennale but my special interest is in the art/sci pieces and, at this point, CRISPR.

Piccinini in more depth

You can find out more about Patricia Piccinini in her biography on the Vancouver Biennale website but I found this Char Larsson April 7, 2018 article for the Independent (UK) more informative (Note: A link has been removed),

Patricia Piccinini’s sculptures are deeply disquieting. Walking through Curious Affection, her new solo exhibition at Brisbane’s Gallery of Modern Art, is akin to entering a science laboratory full of DNA experiments. Made from silicone, fibreglass and even human hair, her sculptures are breathtakingly lifelike, however, we can’t be sure what life they are like. The artist creates an exuberant parallel universe where transgenic experiments flourish and human evolution has given way to genetic engineering and DNA splicing.

Curious Affection is a timely and welcome recognition of Piccinini’s enormous contribution to reaching back to the mid-1990s. Working across a variety of mediums including photography, video and drawing, she is perhaps best known for her hyperreal creations.

As a genre, hyperrealism depends on the skill of the artist to create the illusion of reality. To be truly successful, it must convince the spectator of its realness. Piccinini acknowledges this demand, but with a delightful twist. The excruciating attention to detail deliberately solicits our desire to look, only to generate unease, as her sculptures are imbued with a fascinating otherness. Part human, part animal, the works are uncannily familiar, but also alarmingly “other”.

Inspired by advances in genetically modified pigs to generate replacement organs for humans [also known as xenotransplantation], we are reminded that Piccinini has always been at the forefront of debates concerning the possibilities of science, technology and DNA cloning. She does so, however, with a warm affection and sense of humour, eschewing the hysterical anxiety frequently accompanying these scientific developments.

Beyond the astonishing level of detail achieved by working with silicon and fibreglass, there is an ethics at work here. Piccinini is asking us not to avert our gaze from the other, and in doing so, to develop empathy and understanding through the encounter.

I encourage anyone who’s interested to read Larsson’s entire piece (April 7, 2018 article).

According to her Wikipedia entry, Piccinini works in a variety of media including video, sound, sculpture, and more. She also has her own website.

Gene editing and xenotransplantation

Sarah Zhang’s June 8, 2018 article for The Atlantic provides a peek at the extraordinary degree of interest and competition in the field of gene editing and CRISPR ((clustered regularly interspaced short palindromic repeats))/Cas9 research (Note: A link has been removed),

China Is Genetically Engineering Monkeys With Brain Disorders

Guoping Feng applied to college the first year that Chinese universities reopened after the Cultural Revolution. It was 1977, and more than a decade’s worth of students—5.7 million—sat for the entrance exams. Feng was the only one in his high school to get in. He was assigned—by chance, essentially—to medical school. Like most of his contemporaries with scientific ambitions, he soon set his sights on graduate studies in the United States. “China was really like 30 to 50 years behind,” he says. “There was no way to do cutting-edge research.” So in 1989, he left for Buffalo, New York, where for the first time he saw snow piled several feet high. He completed his Ph.D. in genetics at the State University of New York at Buffalo.

Feng is short and slim, with a monk-like placidity and a quick smile, and he now holds an endowed chair in neuroscience at MIT, where he focuses on the genetics of brain disorders. His 45-person lab is part of the McGovern Institute for Brain Research, which was established in 2000 with the promise of a $350 million donation, the largest ever received by the university. In short, his lab does not lack for much.

Yet Feng now travels to China several times a year, because there, he can pursue research he has not yet been able to carry out in the United States. [emphasis mine] …

Feng had organized a symposium at SIAT [Shenzhen Institutes of Advanced Technology], and he was not the only scientist who traveled all the way from the United States to attend: He invited several colleagues as symposium speakers, including a fellow MIT neuroscientist interested in tree shrews, a tiny mammal related to primates and native to southern China, and Chinese-born neuroscientists who study addiction at the University of Pittsburgh and SUNY Upstate Medical University. Like Feng, they had left China in the ’80s and ’90s, part of a wave of young scientists in search of better opportunities abroad. Also like Feng, they were back in China to pursue a type of cutting-edge research too expensive and too impractical—and maybe too ethically sensitive—in the United States.

Here’s what precipitated Feng’s work in China, (from Zhang’s article; Note: Links have been removed)

At MIT, Feng’s lab worked on genetically engineering a monkey species called marmosets, which are very small and genuinely bizarre-looking. They are cheaper to keep due to their size, but they are a relatively new lab animal, and they can be difficult to train on lab tasks. For this reason, Feng also wanted to study Shank3 on macaques in China. Scientists have been cataloging the social behavior of macaques for decades, making it an obvious model for studies of disorders like autism that have a strong social component. Macaques are also more closely related to humans than marmosets, making their brains a better stand-in for those of humans.

The process of genetically engineering a macaque is not trivial, even with the advanced tools of CRISPR. Researchers begin by dosing female monkeys with the same hormones used in human in vitro fertilization. They then collect and fertilize the eggs, and inject the resulting embryos with CRISPR proteins using a long, thin glass needle. Monkey embryos are far more sensitive than mice embryos, and can be affected by small changes in the pH of the injection or the concentration of CRISPR proteins. Only some of the embryos will have the desired mutation, and only some will survive once implanted in surrogate mothers. It takes dozens of eggs to get to just one live monkey, so making even a few knockout monkeys required the support of a large breeding colony.

The first Shank3 macaque was born in 2015. Four more soon followed, bringing the total to five.

To visit his research animals, Feng now has to fly 8,000 miles across 12 time zones. It would be a lot more convenient to carry out his macaque research in the United States, of course, but so far, he has not been able to.

He originally inquired about making Shank3 macaques at the New England Primate Research Center, one of eight national primate research centers then funded by the National Institutes of Health in partnership with a local institution (Harvard Medical School, in this case). The center was conveniently located in Southborough, Massachusetts, just 20 miles west of the MIT campus. But in 2013, Harvard decided to shutter the center.

The decision came as a shock to the research community, and it was widely interpreted as a sign of waning interest in primate research in the United States. While the national primate centers have been important hubs of research on HIV, Zika, Ebola, and other diseases, they have also come under intense public scrutiny. Animal-rights groups like the Humane Society of the United States have sent investigators to work undercover in the labs, and the media has reported on monkey deaths in grisly detail. Harvard officially made its decision to close for “financial” reasons. But the announcement also came after the high-profile deaths of four monkeys from improper handling between 2010 and 2012. The deaths sparked a backlash; demonstrators showed up at the gates. The university gave itself two years to wind down their primate work, officially closing the center in 2015.

“They screwed themselves,” Michael Halassa, the MIT neuroscientist who spoke at Feng’s symposium, told me in Shenzhen. Wei-Dong Yao, another one of the speakers, chimed in, noting that just two years later CRISPR has created a new wave of interest in primate research. Yao was one of the researchers at Harvard’s primate center before it closed; he now runs a lab at SUNY Upstate Medical University that uses genetically engineered mouse and human stem cells, and he had come to Shenzhen to talk about restarting his addiction research on primates.

Here’s comes the competition (from Zhang’s article; Note: Links have been removed),

While the U.S. government’s biomedical research budget has been largely flat, both national and local governments in China are eager to raise their international scientific profiles, and they are shoveling money into research. A long-rumored, government-sponsored China Brain Project is supposed to give neuroscience research, and primate models in particular, a big funding boost. Chinese scientists may command larger salaries, too: Thanks to funding from the Shenzhen local government, a new principal investigator returning from overseas can get 3 million yuan—almost half a million U.S. dollars—over his or her first five years. China is even finding success in attracting foreign researchers from top U.S. institutions like Yale.

In the past few years, China has seen a miniature explosion of genetic engineering in monkeys. In Kunming, Shanghai, and Guangzhou, scientists have created monkeys engineered to show signs of Parkinson’s, Duchenne muscular dystrophy, autism, and more. And Feng’s group is not even the only one in China to have created Shank3 monkeys. Another group—a collaboration primarily between researchers at Emory University and scientists in China—has done the same.

Chinese scientists’ enthusiasm for CRISPR also extends to studies of humans, which are moving much more quickly, and in some cases under less oversight, than in the West. The first studies to edit human embryos and first clinical trials for cancer therapies using CRISPR have all happened in China. [emphases mine]

Some ethical issues are also covered (from Zhang’s article),

Parents with severely epileptic children had asked him if it would be possible to study the condition in a monkey. Feng told them what he thought would be technically possible. “But I also said, ‘I’m not sure I want to generate a model like this,’” he recalled. Maybe if there were a drug to control the monkeys’ seizures, he said: “I cannot see them seizure all the time.”

But is it ethical, he continued, to let these babies die without doing anything? Is it ethical to generate thousands or millions of mutant mice for studies of brain disorders, even when you know they will not elucidate much about human conditions?

Primates should only be used if other models do not work, says Feng, and only if a clear path forward is identified. The first step in his work, he says, is to use the Shank3 monkeys to identify the changes the mutations cause in the brain. Then, researchers might use that information to find targets for drugs, which could be tested in the same monkeys. He’s talking with the Oregon National Primate Research Center about carrying out similar work in the United States. ….[Note: I have a three-part series about CRISPR and germline editing* in the US, precipitated by research coming out of Oregon, Part 1, which links to the other parts, is here.]

Zhang’s June 8, 2018 article is excellent and I highly recommend reading it.

I touched on the topic of xenotransplanttaion in a commentary on a book about the science  of the television series, Orphan Black in a January 31,2018 posting (Note: A chimera is what you use to incubate a ‘human’ organ for transplantation or, more accurately, xenotransplantation),

On the subject of chimeras, the Canadian Broadcasting Corporation (CBC) featured a January 26, 2017 article about the pig-human chimeras on its website along with a video,

The end

I am very excited to see Piccinini’s work come to Vancouver. There have been a number of wonderful art and art/science installations and discussions here but this is the first one (I believe) to tackle the emerging gene editing technologies and the issues they raise. (It also fits in rather nicely with the 200th anniversary of the publication of Mary Shelley’s Frankenstein which continues to raise issues and stimulate discussion.)

In addition to the ethical issues raised in Zhang’s article, there are some other philosophical questions:

  • what does it mean to be human
  • if we are going to edit genes to create hybrid human/animals, what are they and how do they fit into our current animal/human schema
  • are you still human if you’ve had an organ transplant where the organ was incubated in a pig

There are also going to be legal issues. In addition to any questions about legal status, there are also fights about intellectual property such as the one involving Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley (March 15, 2017 posting)..

While I’m thrilled about the Piccinini installation, it should be noted the issues raised by other artworks hosted in this version of the Biennale are important. Happily, they have been broached here in Vancouver before and I suspect this will result in more nuanced  ‘conversations’ than are possible when a ‘new’ issue is introduced.

Bravo 2018 – 2020 Vancouver Biennale!

* Germline editing is when your gene editing will affect subsequent generations as opposed to editing out a mutated gene for the lifetime of a single individual.

Art/sci and CRISPR links

This art/science posting may prove of some interest:

The connectedness of living things: an art/sci project in Saskatchewan: evolutionary biology (February 16, 2018)

A selection of my CRISPR posts:

CRISPR and editing the germline in the US (part 1 of 3): In the beginning (August 15, 2017)

NOTE: An introductory CRISPR video describing how CRISPR/Cas9 works was embedded in part1.

Why don’t you CRISPR yourself? (January 25, 2018)

Editing the genome with CRISPR ((clustered regularly interspaced short palindromic repeats)-carrying nanoparticles (January 26, 2018)

Immune to CRISPR? (April 10, 2018)

Santiago Ramón y Cajal and the butterflies of the soul

The Cajal exhibit of drawings was here in Vancouver (Canada) this last fall (2017) and I still carry the memory of that glorious experience (see my Sept. 11, 2017 posting for more about the show and associated events). It seems Cajal’s drawings had a similar response in New York city, from a January 18, 2018 article by Roberta Smith for the New York Times,

It’s not often that you look at an exhibition with the help of the very apparatus that is its subject. But so it is with “The Beautiful Brain: The Drawings of Santiago Ramón y Cajal” at the Grey Art Gallery at New York University, one of the most unusual, ravishing exhibitions of the season.

The show finished its run on March 31, 2018 and is now on its way to the Massachusetts Institute of Technology (MIT) in Boston, Massachusetts for its opening on May 3, 2018. It looks like they have an exciting lineup of events to go along with the exhibit (from MIT’s The Beautiful Brain: The Drawings of Santiago Ramón y Cajal exhibit and event page),

SUMMER PROGRAMS

ONGOING

Spotlight Tours
Explorations led by local and Spanish scientists, artists, and entrepreneurs who will share their unique perspectives on particular aspects of the exhibition. (2:00 pm on select Tuesdays and Saturdays)

Tue, May 8 – Mark Harnett, Fred and Carole Middleton Career Development Professor at MIT and McGovern Institute Investigator Sat, May 26 – Marion Boulicault, MIT Graduate Student and Neuroethics Fellow in the Center for Sensorimotor Neural Engineering Tue, June 5 – Kelsey Allen, Graduate researcher, MIT Center for Brains, Minds, and Machines Sat, Jun 23 – Francisco Martin-Martinez, Research Scientist in MIT’s Laboratory for Atomistic & Molecular Mechanics and President of the Spanish Foundation for Science and Technology Jul 21 – Alex Gomez-Marin, Principal Investigator of the Behavior of Organisms Laboratory in the Instituto de Neurociencias, Spain Tue, Jul 31– Julie Pryor, Director of Communications at the McGovern Institute for Brain Research at MIT Tue, Aug 28 – Satrajit Ghosh, Principal Research Scientist at the McGovern Institute for Brain Research at MIT, Assistant Professor in the Department of Otolaryngology at Harvard Medical School, and faculty member in the Speech and Hearing Biosciences and Technology program in the Harvard Division of Medical Sciences

Idea Hub
Drop in and explore expansion microscopy in our maker-space.

Visualizing Science Workshop
Experiential learning with micro-scale biological images. (pre-registration required)

Gallery Demonstrations
Researchers share the latest on neural anatomy, signal transmission, and modern imaging techniques.

EVENTS

Teen Science Café: Mindful Matters
MIT researchers studying the brain share their mind-blowing findings.

Neuron Paint Night
Create a painting of cerebral cortex neurons and learn about the EyeWire citizen science game.

Cerebral Cinema Series
Hear from researchers and then compare real science to depictions on the big screen.

Brainy Trivia
Test your brain power in a night of science trivia and short, snappy research talks.

Come back to see our exciting lineup for the fall!

If you don’t have a chance to see the show or if you’d like a preview, I encourage you to read Smith’s article as it has embedded several Cajal drawings and rendered them exceptionally well.

For those who like a little contemporary (and related) science with their art, there’s a March 30, 2018 Harvard Medical Schoo (HMS)l news release by Kevin Jang (also on EurekAlert), Note: All links save one have been removed,

Drawing of the cells of the chick cerebellum by Santiago Ramón y Cajal, from “Estructura de los centros nerviosos de las aves,” Madrid, circa 1905

 

Modern neuroscience, for all its complexity, can trace its roots directly to a series of pen-and-paper sketches rendered by Nobel laureate Santiago Ramón y Cajal in the late 19th and early 20th centuries.

His observations and drawings exposed the previously hidden composition of the brain, revealing neuronal cell bodies and delicate projections that connect individual neurons together into intricate networks.

As he explored the nervous systems of various organisms under his microscope, a natural question arose: What makes a human brain different from the brain of any other species?

At least part of the answer, Ramón y Cajal hypothesized, lay in a specific class of neuron—one found in a dazzling variety of shapes and patterns of connectivity, and present in higher proportions in the human brain than in the brains of other species. He dubbed them the “butterflies of the soul.”

Known as interneurons, these cells play critical roles in transmitting information between sensory and motor neurons, and, when defective, have been linked to diseases such as schizophrenia, autism and intellectual disability.

Despite more than a century of study, however, it remains unclear why interneurons are so diverse and what specific functions the different subtypes carry out.

Now, in a study published in the March 22 [2018] issue of Nature, researchers from Harvard Medical School, New York Genome Center, New York University and the Broad Institute of MIT and Harvard have detailed for the first time how interneurons emerge and diversify in the brain.

Using single-cell analysis—a technology that allows scientists to track cellular behavior one cell at a time—the team traced the lineage of interneurons from their earliest precursor states to their mature forms in mice. The researchers identified key genetic programs that determine the fate of developing interneurons, as well as when these programs are switched on or off.

The findings serve as a guide for efforts to shed light on interneuron function and may help inform new treatment strategies for disorders involving their dysfunction, the authors said.

“We knew more than 100 years ago that this huge diversity of morphologically interesting cells existed in the brain, but their specific individual roles in brain function are still largely unclear,” said co-senior author Gordon Fishell, HMS professor of neurobiology and a faculty member at the Stanley Center for Psychiatric Research at the Broad.

“Our study provides a road map for understanding how and when distinct interneuron subtypes develop, giving us unprecedented insight into the biology of these cells,” he said. “We can now investigate interneuron properties as they emerge, unlock how these important cells function and perhaps even intervene when they fail to develop correctly in neuropsychiatric disease.”

A hippocampal interneuron. Image: Biosciences Imaging Gp, Soton, Wellcome Trust via Creative CommonsA hippocampal interneuron. Image: Biosciences Imaging Gp, Soton, Wellcome Trust via Creative Commons

Origins and Fates

In collaboration with co-senior author Rahul Satija, core faculty member of the New York Genome Center, Fishell and colleagues analyzed brain regions in developing mice known to contain precursor cells that give rise to interneurons.

Using Drop-seq, a single-cell sequencing technique created by researchers at HMS and the Broad, the team profiled gene expression in thousands of individual cells at multiple time points.

This approach overcomes a major limitation in past research, which could analyze only the average activity of mixtures of many different cells.

In the current study, the team found that the precursor state of all interneurons had similar gene expression patterns despite originating in three separate brain regions and giving rise to 14 or more interneuron subtypes alone—a number still under debate as researchers learn more about these cells.

“Mature interneuron subtypes exhibit incredible diversity. Their morphology and patterns of connectivity and activity are so different from each other, but our results show that the first steps in their maturation are remarkably similar,” said Satija, who is also an assistant professor of biology at New York University.

“They share a common developmental trajectory at the earliest stages, but the seeds of what will cause them to diverge later—a handful of genes—are present from the beginning,” Satija said.

As they profiled cells at later stages in development, the team observed the initial emergence of four interneuron “cardinal” classes, which give rise to distinct fates. Cells were committed to these fates even in the early embryo. By developing a novel computational strategy to link precursors with adult subtypes, the researchers identified individual genes that were switched on and off when cells began to diversify.

For example, they found that the gene Mef2c—mutations of which are linked to Alzheimer’s disease, schizophrenia and neurodevelopmental disorders in humans—is an early embryonic marker for a specific interneuron subtype known as Pvalb neurons. When they deleted Mef2c in animal models, Pvalb neurons failed to develop.

These early genes likely orchestrate the execution of subsequent genetic subroutines, such as ones that guide interneuron subtypes as they migrate to different locations in the brain and ones that help form unique connection patterns with other neural cell types, the authors said.

The identification of these genes and their temporal activity now provide researchers with specific targets to investigate the precise functions of interneurons, as well as how neurons diversify in general, according to the authors.

“One of the goals of this project was to address an incredibly fascinating developmental biology question, which is how individual progenitor cells decide between different neuronal fates,” Satija said. “In addition to these early markers of interneuron divergence, we found numerous additional genes that increase in expression, many dramatically, at later time points.”

The association of some of these genes with neuropsychiatric diseases promises to provide a better understanding of these disorders and the development of therapeutic strategies to treat them, a particularly important notion given the paucity of new treatments, the authors said.

Over the past 50 years, there have been no fundamentally new classes of neuropsychiatric drugs, only newer versions of old drugs, the researchers pointed out.

“Our repertoire is no better than it was in the 1970s,” Fishell said.

“Neuropsychiatric diseases likely reflect the dysfunction of very specific cell types. Our study puts forward a clear picture of what cells to look at as we work to shed light on the mechanisms that underlie these disorders,” Fishell said. “What we will find remains to be seen, but we have new, strong hypotheses that we can now test.”

As a resource for the research community, the study data and software are open-source and freely accessible online.

A gallery of the drawings of Santiago Ramón y Cajal is currently on display in New York City, and will open at the MIT Museum in Boston in May 2018.

Christian Mayer, Christoph Hafemeister and Rachel Bandler served as co-lead authors on the study.

This work was supported by the National Institutes of Health (R01 NS074972, R01 NS081297, MH071679-12, DP2-HG-009623, F30MH114462, T32GM007308, F31NS103398), the European Molecular Biology Organization, the National Science Foundation and the Simons Foundation.

Here’s link to and a citation for the paper,

Developmental diversification of cortical inhibitory interneurons by Christian Mayer, Christoph Hafemeister, Rachel C. Bandler, Robert Machold, Renata Batista Brito, Xavier Jaglin, Kathryn Allaway, Andrew Butler, Gord Fishell, & Rahul Satija. Nature volume 555, pages 457–462 (22 March 2018) doi:10.1038/nature25999 Published: 05 March 2018

This paper is behind a paywall.

Better neuroprostheses for brain diseases and mental illneses

I don’t often get news releases from Sweden but I do on occasion and, sometimes, they even come in their original Swedish versions. In this case, Lund University sent me an English language version about their latest work making brain implants (neural prostheses) safer and effective. From a Sept. 29, 2015 Lund University news release (also on EurekAlert),

Neurons thrive and grow in a new type of nanowire material developed by researchers in Nanophysics and Ophthalmology at Lund University in Sweden. In time, the results might improve both neural and retinal implants, and reduce the risk of them losing their effectiveness over time, which is currently a problem

By implanting electrodes in the brain tissue one can stimulate or capture signals from different areas of the brain. These types of brain implants, or neuro-prostheses as they are sometimes called, are used to treat Parkinson’s disease and other neurological diseases.

They are currently being tested in other areas, such as depression, severe cases of autism, obsessive-compulsive disorders and paralysis. Another research track is to determine whether retinal implants are able to replace light-sensitive cells that die in cases of Retinitis Pigmentosa and other eye diseases.

However, there are severe drawbacks associated with today’s implants. One problem is that the body interprets the implants as foreign objects, resulting in an encapsulation of the electrode, which in turn leads to loss of signal.

One of the researchers explains the approach adopted by the research team (from the news release),

“Our nanowire structure prevents the cells that usually encapsulate the electrodes – glial cells – from doing so”, says Christelle Prinz, researcher in Nanophysics at Lund University in Sweden, who developed this technique together with Maria Thereza Perez, a researcher in Ophthalmology.

“I was very pleasantly surprised by these results. In previous in-vitro experiments, the glial cells usually attach strongly to the electrodes”, she says.

To avoid this, the researchers have developed a small substrate where regions of super thin nanowires are combined with flat regions. While neurons grow and extend processes on the nanowires, the glial cells primarily occupy the flat regions in between.

“The different types of cells continue to interact. This is necessary for the neurons to survive because the glial cells provide them with important molecules.”

So far, tests have only been done with cultured cells (in vitro) but hopefully they will soon be able to continue with experiments in vivo.

The substrate is made from the semiconductor material gallium phosphide where each outgrowing nanowire has a diameter of only 80 nanometres (billionths of a metre).

Here’s a link to and a citation for the paper,

Support of Neuronal Growth Over Glial Growth and Guidance of Optic Nerve Axons by Vertical Nanowire Arrays by Gaëlle Piret, Maria-Thereza Perez, and Christelle N. Prinz. ACS Appl. Mater. Interfaces, 2015, 7 (34), pp 18944–18948 DOI: 10.1021/acsami.5b03798 Publication Date (Web): August 11, 2015

Copyright © 2015 American Chemical Society

This paper appears to be open access as I was able to link to the PDF version.