Tag Archives: UCSD

Controlling agricultural pests with CRISPR-based technology

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CRISPR (clustered regularly interspaced short palindromic repeats) technology is often touted as being ‘precise’, which as far as I can tell, is not exactly the case (see my Nov. 28, 2018 posting about the CRISPR babies [scroll down about 30% of the way for the first hint that CRISPR isn’t]). So, it’s a bit odd to see the word ‘precise’ used as part of a new CRISPR-based technology’s name (from a January 8, 2019 news item on ScienceDaily,

Using the CRISPR gene editing tool, Nikolay Kandul, Omar Akbari and their colleagues at UC San Diego [UC is University of California] and UC Berkeley devised a method of altering key genes that control insect sex determination and fertility.

A description of the new “precision-guided sterile insect technique,” [emphasis mine] or pgSIT, is published Jan. 8 [2019] in the journal Nature Communications.

A January 8, 209 UCSD press release (also on EurekAlert) by Mario Aguilera, which originated the news item, delves further into the research,

When pgSIT-derived eggs are introduced into targeted populations, the researchers report, only adult sterile males emerge, resulting in a novel, environmentally friendly and relatively low-cost method of controlling pest populations in the future.

“CRISPR technology has empowered our team to innovate a new, effective, species-specific, self-limiting, safe and scalable genetic population control technology with remarkable potential to be developed and utilized in a plethora of insect pests and disease vectors,” said Akbari, an assistant professor in UC San Diego’s Division of Biological Sciences. “In the future, we strongly believe this technology will be safely used in the field to suppress and even eradicate target species locally, thereby revolutionizing how insects are managed and controlled going forward.”

Since the 1930s, agricultural researchers have used select methods to release sterile male insects into the wild to control and eradicate pest populations. In the 1950s, a method using irradiated males was implemented in the United States to eliminate the pest species known as the New World Screwworm fly, which consumes animal flesh and causes extensive damage to livestock. Such radiation-based methods were later used in Mexico and parts of Central America and continue today.

Instead of radiation, the new pgSIT (precision-guided sterile insect technique), developed over the past year-and-a-half by Kandul and Akbari in the fruit fly Drosophila, uses CRISPR to simultaneously disrupt key genes that control female viability and male fertility in pest species. pgSIT, the researchers say, results in sterile male progeny with 100 percent efficiency. Because the targeted genes are common to a vast cross-section of insects, the researchers are confident the technology can be applied to a range of insects, including disease-spreading mosquitoes.

The researchers envision a system in which scientists genetically alter and produce eggs of a targeted pest species. The eggs are then shipped to a pest location virtually anywhere in the world, circumventing the need for a production facility on-site. Once the eggs are deployed at the pest location, the researchers say, the newly born sterile males will mate with females in the wild and be incapable of producing offspring, driving down the population.

“This is a novel twist of a very old technology,” said Kandul, an assistant project scientist in UC San Diego’s Division of Biological Sciences. “That novel twist makes it extremely portable from one species to another species to suppress populations of mosquitoes or agricultural pests, for example those that feed on valuable wine grapes.”

The new technology is distinct from continuously self-propagating “gene drive” systems that propagate genetic alterations from generation to generation. Instead, pgSIT is considered a “dead end” since male sterility effectively closes the door on future generations.

“The sterile insect technique is an environmentally safe and proven technology,” [emphasis mine] the researchers note in the paper. “We aimed to develop a novel, safe, controllable, non-invasive genetic CRISPR-based technology that could be transferred across species and implemented worldwide in the short-term to combat wild populations.”

With pgSIT proven in fruit flies, the scientists are hoping to develop the technology in Aedes aegypti, the mosquito species responsible for transmitting dengue fever, Zika, yellow fever and other diseases to millions of people.

“The extension of this work to other insect pests could prove to be a general and very useful strategy to deal with many vector-borne diseases that plague humanity and wreak havoc an agriculture globally,” said Suresh Subramani, global director of the Tata Institute for Genetics and Society.

I have one comment about the ‘safety’ of the sterile insect technique. It’s been safe up until now but, assuming this technique works as described: What happens as this new and more powerful technique is more widely deployed possibly eliminating whole species of insects? Might these ‘pests’ have a heretofore unknown beneficial effect somewhere in the food chain or in an ecosystem? Or, there may be other unintended consequences.

Moving on, here’s a link to and a citation for the paper,

Transforming insect population control with precision guided sterile males with demonstration in flies by Nikolay P. Kandul, Junru Liu, Hector M. Sanchez C., Sean L. Wu, John M. Marshall, & Omar S. Akbari. Nature Communications volume 10, Article number: 84 (2019) DOI: https://doi.org/10.1038/s41467-018-07964-7 Published 08 January 2019

This paper is open access.

The researchers have made this illustrative image available,

Caption: This is a schematic of the new precision-guided sterile insect technique (pgSIT), which uses components of the CRISPR/Cas9 system to disrupt key genes that control female viability and male fertility, resulting in sterile male progeny. Credit: Nikolay Kandul, Akbari Lab, UC San Diego

Alleviating joint damage and inflammation from arthritis with neutrophil nanosponges

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Assuming you’d be happy with limiting the damage for rheumatoid arthritis, at some point in the future, this research looks promisin. Right now it appears the researchers aren’t anywhere close to a clinical trial. From a Sept. 3, 2018 news item on ScienceDaily,

Engineers at the University of California San Diego [UCSD] have developed neutrophil “nanosponges” that can safely absorb and neutralize a variety of proteins that play a role in the progression of rheumatoid arthritis. Injections of these nanosponges effectively treated severe rheumatoid arthritis in two mouse models. Administering the nanosponges early on also prevented the disease from developing.

A Sept. 3, 2018 UCSD press release (also on EurekAlert), which originated the news item, provides more detail,

“Nanosponges are a new paradigm of treatment to block pathological molecules from triggering disease in the body,” said senior author Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering. “Rather than creating treatments to block a few specific types of pathological molecules, we are developing a platform that can block a broad spectrum of them, and this way we can treat and prevent disease more effectively and efficiently.”

This work is one of the latest examples of therapeutic nanosponges developed by Zhang’s lab. Zhang, who is affiliated with the Institute of Engineering in Medicine and Moores Cancer Center at UC San Diego, and his team previously developed red blood cell nanosponges to combat and prevent MRSA infections and macrophage nanosponges to treat and manage sepsis.

neutrophil nanosponge cartoon
Illustration of a neutrophil cell membrane-coated nanoparticle.

The new nanosponges are nanoparticles of biodegradable polymer coated with the cell membranes of neutrophils, a type of white blood cell.

Neutrophils are among the immune system’s first responders against invading pathogens. They are also known to play a role in the development of rheumatoid arthritis, a chronic autoimmune disease that causes painful inflammation in the joints and can ultimately lead to damage of cartilage and bone tissue.

When rheumatoid arthritis develops, cells in the joints produce inflammatory proteins called cytokines. Release of cytokines signals neutrophils to enter the joints. Once there, cytokines bind to receptors on the neutrophil surfaces, activating them to release more cytokines, which in turn draws more neutrophils to the joints and so on.

The nanosponges essentially nip this inflammatory cascade in the bud. By acting as tiny neutrophil decoys, they intercept cytokines and stop them from signaling even more neutrophils to the joints, reducing inflammation and joint damage.

These nanosponges offer a promising alternative to current treatments for rheumatoid arthritis. Some monoclonal antibody drugs, for example, have helped patients manage symptoms of the disease, but they work by neutralizing only specific types of cytokines. This is not sufficient to treat the disease, said Zhang, because there are so many different types of cytokines and pathological molecules involved.

“Neutralizing just one or two types might not be as effective. So our approach is to take neutrophil cell membranes, which naturally have receptors to bind all these different types of cytokines, and use them to manage an entire population of inflammatory molecules,” said Zhang.

“This strategy removes the need to identify specific cytokines or inflammatory signals in the process. Using entire neutrophil cell membranes, we’re cutting off all these inflammatory signals at once,” said first author Qiangzhe Zhang, a Ph.D. student in Professor Liangfang Zhang’s research group at UC San Diego.

To make the neutrophil nanosponges, the researchers first developed a method to separate neutrophils from whole blood. They then processed the cells in a solution that causes them to swell and burst, leaving the membranes behind. The membranes were then broken up into much smaller pieces. Mixing them with ball-shaped nanoparticles made of biodegradable polymer fused the neutrophil cell membranes onto the nanoparticle surfaces.

“One of the major challenges of this work was streamlining this entire process, from isolating neutrophils from blood to removing the membranes, and making this process repeatable. We spent a lot of time figuring this out and eventually created a consistent neutrophil nanosponge production line,” said Qiangzhe Zhang.

In mouse models of severe rheumatoid arthritis, injecting nanosponges in inflamed joints led to reduced swelling and protected cartilage from further damage. The nanosponges performed just as well as treatments in which mice were administered a high dose of monoclonal antibodies.

The nanosponges also worked as a preventive treatment when administered prior to inducing the disease in another group of mice.

Professor Liangfang Zhang cautions that the nanosponge treatment does not eliminate the disease. “We are basically able to manage the disease. It’s not completely gone. But swelling is greatly reduced and cartilage damage is minimized,” he said.

The team hopes to one day see their work in clinical trials.

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

Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis by Qiangzhe Zhang, Diana Dehaini, Yue Zhang, Julia Zhou, Xiangyu Chen, Lifen Zhang, Ronnie H. Fang, Weiwei Gao, & Liangfang Zhang. Nature Nanotechnology (2018) DOI: https://doi.org/10.1038/s41565-018-0254-4 Published 03 September 2018

This paper is behind a paywall.

Transparent graphene electrode technology and complex brain imaging

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Michael Berger has written a May 24, 2018 Nanowerk Spotlight article about some of the latest research on transparent graphene electrode technology and the brain (Note: A link has been removed),

…

In new work, scientists from the labs of Kuzum [Duygu Kuzum, an Assistant Professor of Electrical and Computer Engineering at the University of California, San Diego {UCSD}] and Anna Devor report a transparent graphene microelectrode neural implant that eliminates light-induced artifacts to enable crosstalk-free integration of 2-photon microscopy, optogenetic stimulation, and cortical recordings in the same in vivo experiment. The new class of transparent brain implant is based on monolayer graphene. It offers a practical pathway to investigate neuronal activity over multiple spatial scales extending from single neurons to large neuronal populations.

…

Conventional metal-based microelectrodes cannot be used for simultaneous measurements of multiple optical and electrical parameters, which are essential for comprehensive investigation of brain function across spatio-temporal scales. Since they are opaque, they block the field of view of the microscopes and generate optical shadows impeding imaging.

More importantly, they cause light induced artifacts in electrical recordings, which can significantly interfere with neural signals. Transparent graphene electrode technology presented in this paper addresses these problems and allow seamless and crosstalk-free integration of optical and electrical sensing and manipulation technologies.

In their work, the scientists demonstrate that by careful design of key steps in the fabrication process for transparent graphene electrodes, the light-induced artifact problem can be mitigated and virtually artifact-free local field potential (LFP) recordings can be achieved within operating light intensities.

“Optical transparency of graphene enables seamless integration of imaging, optogenetic stimulation and electrical recording of brain activity in the same experiment with animal models,” Kuzum explains. “Different from conventional implants based on metal electrodes, graphene-based electrodes do not generate any electrical artifacts upon interacting with light used for imaging or optogenetics. That enables crosstalk free integration of three modalities: imaging, stimulation and recording to investigate brain activity over multiple spatial scales extending from single neurons to large populations of neurons in the same experiment.”

The team’s new fabrication process avoids any crack formation in the transfer process, resulting in a 95-100% yield for the electrode arrays. This fabrication quality is important for expanding this technology to high-density large area transparent arrays to monitor brain-scale cortical activity in large animal models or humans.

…

“Our technology is also well-suited for neurovascular and neurometabolic studies, providing a ‘gold standard’ neuronal correlate for optical measurements of vascular, hemodynamic, and metabolic activity,” Kuzum points out. “It will find application in multiple areas, advancing our understanding of how microscopic neural activity at the cellular scale translates into macroscopic activity of large neuron populations.”

“Combining optical techniques with electrical recordings using graphene electrodes will allow to connect the large body of neuroscience knowledge obtained from animal models to human studies mainly relying on electrophysiological recordings of brain-scale activity,” she adds.

Next steps for the team involve employing this technology to investigate coupling and information transfer between different brain regions.

…

This work is part of the US BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative and there’s more than one team working with transparent graphene electrodes. John Hewitt in an Oct. 21, 2014 posting on ExtremeTech describes two other teams’ work (Note: Links have been removed),

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The solution [to the problems with metal electrodes], now emerging from multiple labs throughout the universe is to build flexible, transparent electrode arrays from graphene. Two studies in the latest issue of Nature Communications, one from the University of Wisconsin-Madison and the other from Penn [University of Pennsylvania], describe how to build these devices.

The University of Wisconsin researchers are either a little bit smarter or just a little bit richer, because they published their work open access. It’s a no-brainer then that we will focus on their methods first, and also in more detail. To make the arrays, these guys first deposited the parylene (polymer) substrate on a silicon wafer, metalized it with gold, and then patterned it with an electron beam to create small contact pads. The magic was to then apply four stacked single-atom-thick graphene layers using a wet transfer technique. These layers were then protected with a silicon dioxide layer, another parylene layer, and finally molded into brain signal recording goodness with reactive ion etching.

PennTransparentelectrodeThe researchers went with four graphene layers because that provided optimal mechanical integrity and conductivity while maintaining sufficient transparency. They tested the device in opto-enhanced mice whose neurons expressed proteins that react to blue light. When they hit the neurons with a laser fired in through the implant, the protein channels opened and fired the cell beneath. The masterstroke that remained was then to successfully record the electrical signals from this firing, sit back, and wait for the Nobel prize office to call.

The Penn State group [Note: Every reearcher mentioned in the paper Hewitt linked to is from the University of Pennsylvania] in the  used a similar 16-spot electrode array (pictured above right), and proceeded — we presume — in much the same fashion. Their angle was to perform high-resolution optical imaging, in particular calcium imaging, right out through the transparent electrode arrays which simultaneously recorded in high-temporal-resolution signals. They did this in slices of the hippocampus where they could bring to bear the complex and multifarious hardware needed to perform confocal and two-photon microscopy. These latter techniques provide a boost in spatial resolution by zeroing in over narrow planes inside the specimen, and limiting the background by the requirement of two photons to generate an optical signal. We should mention that there are voltage sensitive dyes available, in addition to standard calcium dyes, which can almost record the fastest single spikes, but electrical recording still reigns supreme for speed.

What a mouse looks like with an optogenetics system plugged in

What a mouse looks like with an optogenetics system plugged in

One concern of both groups in making these kinds of simultaneous electro-optic measurements was the generation of light-induced artifacts in the electrical recordings. This potential complication, called the Becqueral photovoltaic effect, has been known to exist since it was first demonstrated back in 1839. When light hits a conventional metal electrode, a photoelectrochemical (or more simply, a photovoltaic) effect occurs. If present in these recordings, the different signals could be highly disambiguatable. The Penn researchers reported that they saw no significant artifact, while the Wisconsin researchers saw some small effects with their device. In particular, when compared with platinum electrodes put into the opposite side cortical hemisphere, the Wisconsin researchers found that the artifact from graphene was similar to that obtained from platinum electrodes.

…

Here’s a link to and a citation for the latest research from UCSD,

Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays by Martin Thunemann, Yichen Lu, Xin Liu, Kıvılcım Kılıç, Michèle Desjardins, Matthieu Vandenberghe, Sanaz Sadegh, Payam A. Saisan, Qun Cheng, Kimberly L. Weldy, Hongming Lyu, Srdjan Djurovic, Ole A. Andreassen, Anders M. Dale, Anna Devor, & Duygu Kuzum. Nature Communicationsvolume 9, Article number: 2035 (2018) doi:10.1038/s41467-018-04457-5 Published: 23 May 2018

This paper is open access.

You can find out more about the US BRAIN initiative here and if you’re curious, you can find out more about the project at UCSD here. Duygu Kuzum (now at UCSD) was at  the University of Pennsylvania in 2014 and participated in the work mentioned in Hewitt’s 2014 posting.

Acoustic nanomotors deliver Cas9-sgRNA complex to the cell

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The gene editing tool .CRISPR (clustered regularly interspaced short palindromic repeats) does feature in this story but only as a minor character; the real focus is on the delivery system. From a February 9, 2018 news item on Nanowerk ()Note: A link has been removed),

In cancer research, the “Cas-9–sgRNA” complex is an effective genomic editing tool, but its delivery across the cell membrane to the target (tumor) genome has not yet been satisfactorily solved.

American and Danish scientists have now developed an active nanomotor for the efficient transport, delivery, and release of this gene scissoring system. As detailed in their paper in the journal Angewandte Chemie (“Active Intracellular Delivery of a Cas9/sgRNA Complex Using Ultrasound-Propelled Nanomotors”), their nanovehicle is propelled towards its target by ultrasound.

The publisher (Wiley) has made this image illustrating the work available,

Courtesy: Wiley

A February 9, 2018 Wiley Publications news release (also on EurekAlert), which originated the news item, provides more information,

Genomic engineering as a promising cancer therapeutic approach has experienced a tremendous surge since the discovery of the adaptive bacterial immune defense system “CRISPR” and its potential as a gene editing tool over a decade ago. Engineered CRISPR systems for gene editing now contain two main components, a single guide RNA or sgRNA and Cas-9 nuclease. While the sgRNA guides the nuclease to the specified gene sequence, Cas-9 nuclease performs its editing with surgical efficiency. However, the delivery of the large machinery to the target genome is still problematic. The authors of the Angewandte Chemie study, Liangfang Zhang and Joseph Wang from the University of California San Diego, and their colleagues now propose ultrasound-propelled gold nanowires as an active transport/release vehicle for the Cas9-sgRNA complex over the membrane.

Gold nanowires may cross a membrane passively, but thanks to their rod- or wirelike asymmetric shape, active motion can be triggered by ultrasound. “The asymmetric shape of the gold nanowire motor, given by the fabrication process, is essential for the acoustic propulsion,” the authors remarked. They assembled the vehicle by attaching the Cas-9 protein/RNA complex to the gold nanowire through sulfide bridges. These reduceable linkages have the advantage that inside the tumor cell, the bonds would be broken by glutathione, a natural reducing compound enriched in tumor cells. The Cas9-sgRNA would be released and sent to the nucleus to do its editing work, for, example, the knockout of a gene.

As a test system, the scientists monitored the suppression of fluorescence emitted by green fluorescence protein expressing melanoma B16F10 cells. Ultrasound was applied for five minutes, which accelerated the nanomotor carrying the Cas9-sgRNA complex across the membrane, accelerating it even inside the cell, as the authors noted. Moreover, they observed their Cas9-sgRNA complex effectively suppressing fluorescence with only tiny concentrations of the complex needed.

Thus, both the effective use of an acoustic nanomotor as an active transporter and the small payload needed for efficient gene knockout are intriguing results of the study. The simplicity of the system, which uses only few and readily available components, is another remarkable achievement.

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

Active Intracellular Delivery of a Cas9/sgRNA Complex Using Ultrasound-Propelled Nanomotors by Malthe Hansen-Bruhn, Dr. Berta Esteban-Fernández de Ávila, Dr. Mara Beltrán-Gastélum, Prof. Jing Zhao, Dr. Doris E. Ramírez-Herrera, Pavimol Angsantikul, Prof. Kurt Vesterager Gothelf, Prof. Liangfang Zhang, and Prof. Joseph Wang. Angewandte Chemie International Edition Vol. 57 Issue 7 DOI: 10.1002/anie.201713082 Version of Record online: 6 FEB 2018

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

The ultimate natural sunscreen

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For those of us in the northern hemisphere, sunscreen season is on the horizon. While the “ultimate natural sunscreen” researchers from the University of California at San Diego (UCSD) have developed is a long way from the marketplace, this is encouraging news (from a May 17, 2017 news item on Nanowerk),

Chemists, materials scientists and nanoengineers at UC San Diego have created what may be the ultimate natural sunscreen.

In a paper published in the American Chemical Society journal ACS Central Science, they report the development of nanoparticles that mimic the behavior of natural melanosomes, melanin-producing cell structures that protect our skin, eyes and other tissues from the harmful effects of ultraviolet radiation.

“Basically, we succeeded in making a synthetic version of the nanoparticles that our skin uses to produce and store melanin and demonstrated in experiments in skin cells that they mimic the behavior of natural melanosomes,” said Nathan Gianneschi, a professor of chemistry and biochemistry, materials science and engineering and nanoengineering at UC San Diego, who headed the team of researchers. The achievement has practical applications.

A May 17, 2017 UCSD news release, which originated the news item, delves into the research,

“Defects in melanin production in humans can cause diseases such as vitiligo and albinism that lack effective treatments,” Gianneschi added.

Vitiligo develops when the immune system wrongly attempts to clear normal melanocytes from the skin, effectively stopping the production of melanocytes. Albinism is due to genetic defects that lead to either the absence or a chemical defect in tyrosinase, a copper-containing enzyme involved in the production of melanin. Both of these diseases lack effective treatments and result in a significant risk of skin cancer for patients.

“The widespread prevalence of these melanin-related diseases and an increasing interest in the performance of various polymeric materials related to melanin prompted us to look for novel synthetic routes for preparing melanin-like materials,” Gianneschi said.

UC San Diego Ultimate natural sunscreenThe scientists found that the synthetic nanoparticles were taken up in tissue culture by keratinocytes, the predominant cell type found in the epidermis, the outer layer of skin. Photo by Yuran Huang and Ying Jones/UC San Diego

Melanin particles are produced naturally in many different sizes and shapes by animals—for iridescent feathers in birds or the pigmented eyes and skin of some reptiles. But scientists have discovered that extracting melanins from natural sources is a difficult and potentially more complex process than producing them synthetically.

Gianneschi and his team discovered two years ago that synthetic melanin-like nanoparticles could be developed in a precisely controllable manner to mimic the performance of natural melanins used in bird feathers.

“We hypothesized that synthetic melanin-like nanoparticles would mimic naturally occurring melanosomes and be taken up by keratinocytes, the predominant cell type found in the epidermis, the outer layer of skin,” said Gianneschi.

In healthy humans, melanin is delivered to keratinocytes in the skin after being excreted as melanosomes from melanocytes.

The UC San Diego scientists prepared melanin-like nanoparticles through the spontaneous oxidation of dopamine—developing biocompatible, synthetic analogues of naturally occurring melanosomes. Then they studied their update, transport, distribution and ultraviolet radiation-protective capabilities in human keratinocytes in tissue culture.

The researchers found that these synthetic nanoparticles were not only taken up and distributed normally, like natural melanosomes, within the keratinocytes, they protected the skin cells from DNA damage due to ultraviolet radiation.

“Considering limitations in the treatment of melanin-defective related diseases and the biocompatibility of these synthetic melanin-like nanoparticles in terms of uptake and degradation, these systems have potential as artificial melanosomes for the development of novel therapies, possibly supplementing the biological functions of natural melanins,” the researchers said in their paper.

The other co-authors of the study were Yuran Huang and Ziying Hu of UC San Diego’s Materials Science and Engineering Program, Yiwen Li and Maria Proetto of the Department of Chemistry and Biochemistry; Xiujun Yue of the Department of Nanoengineering; and Ying Jones of the Electron Microscopy Core Facility.

The UC San Diego Office of Innovation and Commercialization has filed a patent application on the use of polydopamine-based artificial melanins as an intracellular UV-shield. Companies interested in commercializing this invention should contact Skip Cynar at invent@ucsd.edu

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

Mimicking Melanosomes: Polydopamine Nanoparticles as Artificial Microparasols by
Yuran Huang, Yiwen Li, Ziying Hu, Xiujun Yue, Maria T. Proetto, Ying Jones, and Nathan C. Gianneschi. ACS Cent. Sci., Article ASAP DOI: 10.1021/acscentsci.6b00230 Publication Date (Web): May 18, 2017

Copyright © 2017 American Chemical Society

This is an open access paper,

Using CRISPR to reverse retinosa pigmentosa (eye disease)

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Years ago I worked as a publicist for the BC (British Columbia) Motorcycle Federation’s Ride for Sight; they were raising funds for research into retinitis pigmentosa (RP). I hadn’t thought about that in years but it all came back when I saw this April 21, 2017 news item on ScienceDaily,

Using the gene-editing tool CRISPR/Cas9, researchers at University of California San Diego [UCSD] School of Medicine and Shiley Eye Institute at UC San Diego Health, with colleagues in China, have reprogrammed mutated rod photoreceptors to become functioning cone photoreceptors, reversing cellular degeneration and restoring visual function in two mouse models of retinitis pigmentosa.

Caption: This is a confocal micrograph of mouse retina depicting optic fiber layer. Credit: Image courtesy of National Center for Microscopy and Imaging Research, UC San Diego.

An April 21, 2017 UCSD news release by Scott LaFee (also on EurekAlert), which originated the news item, delves further into retinitis pigmentosa and this CRISPR research,

Retinitis pigmentosa (RP) is a group of inherited vision disorders caused by numerous mutations in more than 60 genes. The mutations affect the eyes’ photoreceptors, specialized cells in the retina that sense and convert light images into electrical signals sent to the brain. There are two types: rod cells that function for night vision and peripheral vision, and cone cells that provide central vision (visual acuity) and discern color. The human retina typically contains 120 million rod cells and 6 million cone cells.

In RP, which affects approximately 100,000 Americans and 1 in 4,000 persons worldwide, rod-specific genetic mutations cause rod photoreceptor cells to dysfunction and degenerate over time. Initial symptoms are loss of peripheral and night vision, followed by diminished visual acuity and color perception as cone cells also begin to fail and die. There is no treatment for RP. The eventual result may be legal blindness.

In their published research, a team led by senior author Kang Zhang, MD, PhD, chief of ophthalmic genetics, founding director of the Institute for Genomic Medicine and co-director of biomaterials and tissue engineering at the Institute of Engineering in Medicine, both at UC San Diego School of Medicine, used CRISPR/Cas9 to deactivate a master switch gene called Nrl and a downstream transcription factor called Nr2e3.

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, allows researchers to target specific stretches of genetic code and edit DNA at precise locations, modifying select gene functions. Deactivating either Nrl or Nr2e3 reprogrammed rod cells to become cone cells.

“Cone cells are less vulnerable to the genetic mutations that cause RP,” said Zhang. “Our strategy was to use gene therapy to make the underlying mutations irrelevant, resulting in the preservation of tissue and vision.”

The scientists tested their approach in two different mouse models of RP. In both cases, they found an abundance of reprogrammed cone cells and preserved cellular architecture in the retinas. Electroretinography testing of rod and cone receptors in live mice show improved function.

Zhang said a recent independent study led by Zhijian Wu, PhD, at National Eye Institute, part of the National Institutes of Health, also reached similar conclusions.

The researchers used adeno-associated virus (AAV) to perform the gene therapy, which they said should help advance their work to human clinical trials quicker. “AAV is a common cold virus and has been used in many successful gene therapy treatments with a relatively good safely profile,” said Zhang. “Human clinical trials could be planned soon after completion of preclinical study. There is no treatment for RP so the need is great and pressing. In addition, our approach of reprogramming mutation-sensitive cells to mutation-resistant cells may have broader application to other human diseases, including cancer.”

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

Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors by Jie Zhu, Chang Ming, Xin Fu, Yaou Duan, Duc Anh Hoang, Jeffrey Rutgard, Runze Zhang, Wenqiu Wang, Rui Hou, Daniel Zhang, Edward Zhang, Charlotte Zhang, Xiaoke Hao, Wenjun Xiong, and Kang Zhang. Cell Research advance online publication 21 April 2017; doi: 10.1038/cr.2017.57

This paper (it’s in the form of a letter to the editor) is open access.

The insanity of Canadian science outreach (Science Odyssey, May 12 – 21, 2017 and Science RendezVous on May 13, 2017)

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When was the last time you saw a six-year old or a twelve-year old attend a political candidates’ meeting or vote in an election? Sadly, most creative science outreach in Canada is aimed at children and teenagers in the misbegotten belief that adults don’t matter and ‘youth are the future’. There are three adult science outreach scenarios although they didn’t tend to be particularly creative. (1) Should scientists feel hard done by elected representatives, they reach out to other adults for support. (2) Should those other adults become disturbed by any scientific or technological ‘advance’ then scientific experts will arrive to explain why that’s wrong. (3) Should the science enterprise want money, then a call goes out (see my May 12, 2017 posting about the Canada Science and Technology Museums Corporation gala and, yes, they were a bit creative about it).

I am oversimplifying the situation but not by much especially if one considers two upcoming national Canadian science events: Science Rendezvous which is a day-long (May 13, 2017) cross country science event taking place during while the Science Odyssey holds a 10-day (May 12 – 2017) cross country science event. The two groups arranged their events separately and then decided to coordinate their efforts. Science Odyssey is a rebranding of the Canada Science and Technology Week organized by the federal government for at least two decades and which was held (until 2016) in the fall of each year. Science Rendezvous (About page) was launched in Toronto in 2008 (University of Toronto, Ryerson University, York University and the University of Ontario Institute of Technology (UOIT)).

Regardless, both events are clearly aimed at children (and families).

I’m not suggesting that exciting science outreach for children should be curtailed. Let’s expand the efforts to9 include the adult and senior populations too.

In all the talk about Canada’s adult and ageing populations, perhaps we could approach it all more creatively. For example, there’s this (from an April 18, 2017 University of California at San Diego University news release (also on EurekAlert) by Inga Kiderra,

IMAGE
IMAGE: Philip Guo surveyed adults between the ages of 60 and 85 who were users of pythontutor.com and learning how to code. They were mix of retired, semi-retired and still working. Credit: Courtesy Philip Guo, UC San Diego

Philip Guo caught the coding bug in high school, at a fairly typical age for a Millennial. Less typical is that the UC San Diego cognitive scientist is now eager to share his passion for programming with a different demographic. And it’s not one you’re thinking of – it’s not elementary or middle school-aged kids. Guo wants to get adults age 60 and up.

In the first known study of older adults learning computer programming, Guo outlines his reasons: People are living and working longer. This is a growing segment of the population, and it’s severely underserved by learn-to-code intiatives, which usually target college students and younger. Guo wants to change that. He would like this in-demand skill to become more broadly accessible.

“Computers are everywhere, and digital literacy is becoming more and more important,” said Guo, assistant professor in the Department of Cognitive Science, who is also affiliated with UC San Diego’s Design Lab and its Department of Computer Science and Engineering. “At one time, 1,000 years ago, most people didn’t read or write – just some monks and select professionals could do it. I think in the future people will need to read and write in computer language as well. In the meantime, more could benefit from learning how to code.”

Guo’s study was recently awarded honorable mention by the world’s leading organization in human-computer interaction, ACM SIGCHI. Guo will present his findings at the group’s premier international conference, CHI, in May [2017].

When prior human-computer interaction studies have focused on older adults at all, Guo said, it has been mostly as consumers of new technology, of social networking sites like Facebook, say, or ride-sharing services. While a few have investigated the creation of content, like blogging or making digital music, these have involved the use of existing apps. None, to his knowledge, have looked at older adults as makers of entirely new software applications, so he set out to learn about their motivations, their frustrations and if these provided clues to design opportunities.

The Study

For his study, Guo surveyed users of pythontutor.com. A web-based education tool that Guo started in 2010, Python Tutor helps those learning to program visualize their work. Step by step, it displays what a computer is doing with each line of code that it runs. More than 3.5 million people in more than 180 countries have now used Python Tutor, including those around the world taking MOOCs (massive open online courses). Despite its legacy name, the tool helps people supplement their studies not only of the Python programming language but also Java, JavaScript, Ruby, C and C++, all of which are commonly used to teach programing. The users of Python Tutor represent a wide range of demographic groups.

Guo’s survey included 504 people between the ages of 60 and 85, from 52 different countries. Some were retired and semi-retired while others were still working.

What Guo discovered: Older adults are motivated to learn programming for a number of reasons. Some are age-related. They want to make up for missed opportunities during youth (22 percent) and keep their brains “challenged, fresh and sharp” as they age (19 percent). A few (5 percent) want to connect with younger family members.

Reasons not related to age include seeking continuing education for a current job (14 percent) and wanting to improve future job prospects (9 percent). A substantial group is in it just for personal enrichment: 19 percent to implement a specific hobby project idea, 15 percent for fun and entertainment, and 10 percent out of general interest.

Interestingly, 8 percent said they wanted to learn to teach others.

Topping the list of frustrations for older students of coding was bad pedagogy. It was mentioned by 21 percent of the respondents and ranged from the use of jargon to sudden spikes in difficulty levels. Lack of real-world relevance came up 6 percent of the time. A 74-year-old retired physician wrote: “Most [tutorials] are offered by people who must know how to program but don’t seem to have much training in teaching.”

Other frustrations included a perceived decline in cognitive abilities (12 percent) and no human contact with tutors and peers (10 percent).

The study’s limitations are tied in part to the instrument – self-reporting on an online survey – and in part to the survey respondents themselves. Most hailed from North America and other English-speaking nations. Most, 84 percent, identified themselves as male; this stat is consistent with other surveys of online learning, especially in math and science topics. There was a diverse array of occupations reported, but the majority of those surveyed were STEM professionals, managers and technicians. These learners, Guo said, likely represent “early adopters” and “the more technology-literate and self-motivated end of the general population.” He suggests future studies look both at in-person learning and at a broader swath of the public. But he expects the lessons learned from this group will generalize.

The Implications

Based on this first set of findings and using a learner-centered design approach, Guo proposes tailoring computer-programming tools and curricula specifically for older learners. He notes, for example, that many of his respondents seemed to take pride in their years and in their tech-savvy, so while it may be good to advertise products as targeting this age group, they should not appear patronizing. It might make sense to reframe lessons as brain-training games, like Lumosity, now popular among the older set.

Just as it’s key to understand who the learners are so is understanding where they have trouble. Repetition and frequent examples might be good to implement, as well as more in-person courses or video-chat-based workshops, Guo said, which may lead to improvements in the teaching of programming not just for older adults but across the board.

Context matters, too. Lessons are more compelling when they are put into domains that people personally care about. And Guo recommends coding curricula that enable older adults to tell their life stories or family histories, for example, or write software that organizes health information or assists care-givers.

Guo, who is currently working on studies to extend coding education to other underrepresented groups, advocates a computing future that is fully inclusive of all ages.

“There are a number of social implications when older adults have access to computer programming – not merely computer literacy,” he said. “These range from providing engaging mental stimulation to greater gainful employment from the comfort of one’s home.”

By moving the tech industry away from its current focus on youth, Guo argues, we all stand to gain. [emphasis mine]

Guo joined the UC San Diego cognitive science faculty in 2016 after two years as an assistant professor at the University of Rochester. He received his bachelor’s and master’s degrees in computer science from MIT in 2006 and his Ph.D. from Stanford in 2012. Before becoming a professor, he built online learning tools as a software engineer at Google and a research scientist at edX. He also blogs, vlogs and podcasts at http://pgbovine.net/

When was the last time you heard about a ‘coding’ camp for adults and seniors in Canada? Also,, ask yourself if after you’d reached a certain age (40? 50? more? less?) you’d feel welcome at the Science Rendezvous events (without a child in tow), Science Odyssey events (without a child in tow), or the May 17, 2017 National Science and Innovation Gala in Ottawa (from my May 12, 2017 posting “It would seem the only person over the age of 30 who’s expected to attend is the CBC host, Heather Hiscox.”)?

Let’s open the door a bit wider, eh?

A new class of artificial retina

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If I read the news release rightly (keep scrolling), this particular artificial retina does not require a device outside the body (e.g. specially developed eyeglasses) to capture an image to be transmitted to the implant. This new artificial retina captures the image directly.

The announcement of a new artificial retina is made in a March 13, 2017 news item on Nanowerk (Note: A link has been removed),

A team of engineers at the University of California San Diego and La Jolla-based startup Nanovision Biosciences Inc. have developed the nanotechnology and wireless electronics for a new type of retinal prosthesis that brings research a step closer to restoring the ability of neurons in the retina to respond to light. The researchers demonstrated this response to light in a rat retina interfacing with a prototype of the device in vitro.

They detail their work in a recent issue of the Journal of Neural Engineering (“Towards high-resolution retinal prostheses with direct optical addressing and inductive telemetry”). The technology could help tens of millions of people worldwide suffering from neurodegenerative diseases that affect eyesight, including macular degeneration, retinitis pigmentosa and loss of vision due to diabetes

Caption: These are primary cortical neurons cultured on the surface of an array of optoelectronic nanowires. Here a neuron is pulling the nanowires, indicating the the cell is doing well on this material. Credit: UC San Diego

A March 13, 2017 University of California at San Diego (UCSD) news release (also on EurekAlert) by Ioana Patringenaru, which originated the news item, details the new approach,

Despite tremendous advances in the development of retinal prostheses over the past two decades, the performance of devices currently on the market to help the blind regain functional vision is still severely limited–well under the acuity threshold of 20/200 that defines legal blindness.

“We want to create a new class of devices with drastically improved capabilities to help people with impaired vision,” said Gabriel A. Silva, one of the senior authors of the work and professor in bioengineering and ophthalmology at UC San Diego. Silva also is one of the original founders of Nanovision.

The new prosthesis relies on two groundbreaking technologies. One consists of arrays of silicon nanowires that simultaneously sense light and electrically stimulate the retina accordingly. The nanowires give the prosthesis higher resolution than anything achieved by other devices–closer to the dense spacing of photoreceptors in the human retina. The other breakthrough is a wireless device that can transmit power and data to the nanowires over the same wireless link at record speed and energy efficiency.

One of the main differences between the researchers’ prototype and existing retinal prostheses is that the new system does not require a vision sensor outside of the eye [emphasis mine] to capture a visual scene and then transform it into alternating signals to sequentially stimulate retinal neurons. Instead, the silicon nanowires mimic the retina’s light-sensing cones and rods to directly stimulate retinal cells. Nanowires are bundled into a grid of electrodes, directly activated by light and powered by a single wireless electrical signal. This direct and local translation of incident light into electrical stimulation makes for a much simpler–and scalable–architecture for the prosthesis.

The power provided to the nanowires from the single wireless electrical signal gives the light-activated electrodes their high sensitivity while also controlling the timing of stimulation.

“To restore functional vision, it is critical that the neural interface matches the resolution and sensitivity of the human retina,” said Gert Cauwenberghs, a professor of bioengineering at the Jacobs School of Engineering at UC San Diego and the paper’s senior author.

Wireless telemetry system

Power is delivered wirelessly, from outside the body to the implant, through an inductive powering telemetry system developed by a team led by Cauwenberghs.

The device is highly energy efficient because it minimizes energy losses in wireless power and data transmission and in the stimulation process, recycling electrostatic energy circulating within the inductive resonant tank, and between capacitance on the electrodes and the resonant tank. Up to 90 percent of the energy transmitted is actually delivered and used for stimulation, which means less RF wireless power emitting radiation in the transmission, and less heating of the surrounding tissue from dissipated power.

The telemetry system is capable of transmitting both power and data over a single pair of inductive coils, one emitting from outside the body, and another on the receiving side in the eye. The link can send and receive one bit of data for every two cycles of the 13.56 megahertz RF signal; other two-coil systems need at least 5 cycles for every bit transmitted.

Proof-of-concept test

For proof-of-concept, the researchers inserted the wirelessly powered nanowire array beneath a transgenic rat retina with rhodopsin P23H knock-in retinal degeneration. The degenerated retina interfaced in vitro with a microelectrode array for recording extracellular neural action potentials (electrical “spikes” from neural activity).

The horizontal and bipolar neurons fired action potentials preferentially when the prosthesis was exposed to a combination of light and electrical potential–and were silent when either light or electrical bias was absent, confirming the light-activated and voltage-controlled responsivity of the nanowire array.

The wireless nanowire array device is the result of a collaboration between a multidisciplinary team led by Cauwenberghs, Silva and William R. Freeman, director of the Jacobs Retina Center at UC San Diego, UC San Diego electrical engineering professor Yu-Hwa Lo and Nanovision Biosciences.

A path to clinical translation

Freeman, Silva and Scott Thorogood, have co-founded La Jolla-based Nanovision Biosciences, a partner in this study, to further develop and translate the technology into clinical use, with the goal of restoring functional vision in patients with severe retinal degeneration. Animal tests with the device are in progress, with clinical trials following.

“We have made rapid progress with the development of the world’s first nanoengineered retinal prosthesis as a result of the unique partnership we have developed with the team at UC San Diego,” said Thorogood, who is the CEO of Nanovision Biosciences.

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

Towards high-resolution retinal prostheses with direct optical addressing and inductive telemetry by Sohmyung Ha, Massoud L Khraiche, Abraham Akinin, Yi Jing, Samir Damle, Yanjin Kuang, Sue Bauchner, Yu-Hwa Lo, William R Freeman, Gabriel A Silva.Journal of Neural Engineering, Volume 13, Number 5 DOI: https://doi.org/10.1088/1741-2560/13/5/056008

Published 16 August 2016 • © 2016 IOP Publishing Ltd

I’m not sure why they waited so long to make the announcement but, in any event, this paper is behind a paywall.

3D printed biomimetic blood vessel networks

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An artificial blood vessel network that could lead the way to regenerating biologically-based blood vessel networks has been printed in 3D at the University of California at San Diego (UCSD) according to a March 2, 2017 news item on ScienceDaily,

Nanoengineers at the University of California San Diego have 3D printed a lifelike, functional blood vessel network that could pave the way toward artificial organs and regenerative therapies.

The new research, led by nanoengineering professor Shaochen Chen, addresses one of the biggest challenges in tissue engineering: creating lifelike tissues and organs with functioning vasculature — networks of blood vessels that can transport blood, nutrients, waste and other biological materials — and do so safely when implanted inside the body.

A March 2, 2017 UCSD news release (also on EurekAlert), which originated the news item, explains why this is an important development,

Researchers from other labs have used different 3D printing technologies to create artificial blood vessels. But existing technologies are slow, costly and mainly produce simple structures, such as a single blood vessel — a tube, basically. These blood vessels also are not capable of integrating with the body’s own vascular system.

“Almost all tissues and organs need blood vessels to survive and work properly. This is a big bottleneck in making organ transplants, which are in high demand but in short supply,” said Chen, who leads the Nanobiomaterials, Bioprinting, and Tissue Engineering Lab at UC San Diego. “3D bioprinting organs can help bridge this gap, and our lab has taken a big step toward that goal.”

Chen’s lab has 3D printed a vasculature network that can safely integrate with the body’s own network to circulate blood. These blood vessels branch out into many series of smaller vessels, similar to the blood vessel structures found in the body. The work was published in Biomaterials.

Chen’s team developed an innovative bioprinting technology, using their own homemade 3D printers, to rapidly produce intricate 3D microstructures that mimic the sophisticated designs and functions of biological tissues. Chen’s lab has used this technology in the past to create liver tissue and microscopic fish that can swim in the body to detect and remove toxins.

Researchers first create a 3D model of the biological structure on a computer. The computer then transfers 2D snapshots of the model to millions of microscopic-sized mirrors, which are each digitally controlled to project patterns of UV light in the form of these snapshots. The UV patterns are shined onto a solution containing live cells and light-sensitive polymers that solidify upon exposure to UV light. The structure is rapidly printed one layer at a time, in a continuous fashion, creating a 3D solid polymer scaffold encapsulating live cells that will grow and become biological tissue.

“We can directly print detailed microvasculature structures in extremely high resolution. Other 3D printing technologies produce the equivalent of ‘pixelated’ structures in comparison and usually require sacrificial materials and additional steps to create the vessels,” said Wei Zhu, a postdoctoral scholar in Chen’s lab and a lead researcher on the project.

And this entire process takes just a few seconds — a vast improvement over competing bioprinting methods, which normally take hours just to print simple structures. The process also uses materials that are inexpensive and biocompatible.

Chen’s team used medical imaging to create a digital pattern of a blood vessel network found in the body. Using their technology, they printed a structure containing endothelial cells, which are cells that form the inner lining of blood vessels.

The entire structure fits onto a small area measuring 4 millimeters × 5 millimeters, 600 micrometers thick (as thick as a stack containing 12 strands of human hair).

Researchers cultured several structures in vitro for one day, then grafted the resulting tissues into skin wounds of mice. After two weeks, the researchers examined the implants and found that they had successfully grown into and merged with the host blood vessel network, allowing blood to circulate normally.

Chen noted that the implanted blood vessels are not yet capable of other functions, such as transporting nutrients and waste. “We still have a lot of work to do to improve these materials. This is a promising step toward the future of tissue regeneration and repair,” he said.

Moving forward, Chen and his team are working on building patient-specific tissues using human induced pluripotent stem cells, which would prevent transplants from being attacked by a patient’s immune system. And since these cells are derived from a patient’s skin cells, researchers won’t need to extract any cells from inside the body to build new tissue. The team’s ultimate goal is to move their work to clinical trials. “It will take at least several years before we reach that goal,” Chen said.

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

Direct 3D bioprinting of prevascularized tissue constructs with complex microarchitecture by Wei Zhu, Xin Qu, Jie Zhu, Xuanyi Ma, Sherrina Patel, Justin Liu, Pengrui Wang, Cheuk Sun Edwin Lai, Maling Gou, Yang Xu, Kang Zhang, Shaochen Chen. Biomaterials 124 (April 2017) 106-15 http://dx.doi.org/10.1016/j.biomaterials.2017.01.042

This paper is behind a paywall.

There is also an open access copy here on the university website but I cannot confirm that it is identical to the version in the journal.

Hairy strength could lead to new body armour

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A Jan. 18, 2017 news item on Nanowerk announces research into hair strength from the University of California at San Diego (UCSD or UC San Diego),

In a new study, researchers at the University of California San Diego investigate why hair is incredibly strong and resistant to breaking. The findings could lead to the development of new materials for body armor and help cosmetic manufacturers create better hair care products.

Hair has a strength to weight ratio comparable to steel. It can be stretched up to one and a half times its original length before breaking. “We wanted to understand the mechanism behind this extraordinary property,” said Yang (Daniel) Yu, a nanoengineering Ph.D. student at UC San Diego and the first author of the study.

A Jan. 18 (?), 2017 UCSD news release, which originated the news item, provides more information,

“Nature creates a variety of interesting materials and architectures in very ingenious ways. We’re interested in understanding the correlation between the structure and the properties of biological materials to develop synthetic materials and designs — based on nature — that have better performance than existing ones,” said Marc Meyers, a professor of mechanical engineering at the UC San Diego Jacobs School of Engineering and the lead author of the study.

In a study published online in Dec. in the journal Materials Science and Engineering C, researchers examined at the nanoscale level how a strand of human hair behaves when it is deformed, or stretched. The team found that hair behaves differently depending on how fast or slow it is stretched. The faster hair is stretched, the stronger it is. “Think of a highly viscous substance like honey,” Meyers explained. “If you deform it fast it becomes stiff, but if you deform it slowly it readily pours.”

Hair consists of two main parts — the cortex, which is made up of parallel fibrils, and the matrix, which has an amorphous (random) structure. The matrix is sensitive to the speed at which hair is deformed, while the cortex is not. The combination of these two components, Yu explained, is what gives hair the ability to withstand high stress and strain.

And as hair is stretched, its structure changes in a particular way. At the nanoscale, the cortex fibrils in hair are each made up of thousands of coiled spiral-shaped chains of molecules called alpha helix chains. As hair is deformed, the alpha helix chains uncoil and become pleated sheet structures known as beta sheets. This structural change allows hair to handle a large amount deformation without breaking.

This structural transformation is partially reversible. When hair is stretched under a small amount of strain, it can recover its original shape. Stretch it further, the structural transformation becomes irreversible. “This is the first time evidence for this transformation has been discovered,” Yu said.

“Hair is such a common material with many fascinating properties,” said Bin Wang, a UC San Diego PhD alumna from the Department of Mechanical and Aerospace Engineering and co-author on the paper. Wang is now at the Shenzhen Institutes of Advanced Technology in China continuing research on hair.

The team also conducted stretching tests on hair at different humidity levels and temperatures. At higher humidity levels, hair can withstand up to 70 to 80 percent deformation before breaking (dry hair can undergo up to 50 percent deformation). Water essentially “softens” hair — it enters the matrix and breaks the sulfur bonds connecting the filaments inside a strand of hair. Researchers also found that hair starts to undergo permanent damage at 60 degrees Celsius (140 degrees Fahrenheit). Beyond this temperature, hair breaks faster at lower stress and strain.

“Since I was a child I always wondered why hair is so strong. Now I know why,” said Wen Yang, a former postdoctoral researcher in Meyers’ research group and co-author on the paper.

The team is currently conducting further studies on the effects of water on the properties of human hair. Moving forward, the team is investigating the detailed mechanism of how washing hair causes it to return to its original shape.

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

Structure and mechanical behavior of human hair by Yang Yua, Wen Yang, Bin Wang, Marc André Meyers. Materials Science and Engineering: C Volume 73, 1 April 2017, Pages 152–163    http://dx.doi.org/10.1016/j.msec.2016.12.008

This paper is behind a paywall.