Tag Archives: flies

The latest and greatest in gene drives (for flies)

This is a CRISPR (clustered regularly interspaced short palindromic repeats) story where the researchers are working on flies. If successful, this has much wider implications. From an April 10, 2019 news item on phys.org,

New CRISPR-based gene drives and broader active genetics technologies are revolutionizing the way scientists engineer the transfer of specific traits from one generation to another.

Scientists at the University of California San Diego have now developed a new version of a gene drive that opens the door to the spread of specific, favorable subtle genetic variants, also known as “alleles,” throughout a population.

The new “allelic drive,” described April 9 [2019] in Nature Communications, is equipped with a guide RNA (gRNA) that directs the CRISPR system to cut undesired variants of a gene and replace it with a preferred version of the gene. The new drive extends scientists’ ability to modify populations of organisms with precision editing. Using word processing as an analogy, CRISPR-based gene drives allow scientists to edit sentences of genetic information, while the new allelic drive offers letter-by-letter editing.

An April 9, 2019 University of California at San Diego (UCSD) news release (also on EurekAlert) by Mario Aguilera, which originated the news item, delves into this technique’s potential uses while further explaining the work

In one example of its potential applications, specific genes in agricultural pests that have become resistant to insecticides could be replaced by original natural genetic variants conferring sensitivity to insecticides using allelic drives that selectively swap the identities of a single protein residue (amino acid).

In addition to agricultural applications, disease-carrying insects could be a target for allelic drives.

“If we incorporate such a normalizing gRNA on a gene-drive element, for example, one designed to immunize mosquitoes against malaria, the resulting allelic gene drive will spread through a population. When this dual action drive encounters an insecticide-resistant allele, it will cut and repair it using the wild-type susceptible allele,” said Ethan Bier, the new paper’s senior author. “The result being that nearly all emerging progeny will be sensitive to insecticides as well as refractory to malaria transmission.”

“Forcing these species to return to their natural sensitive state using allelic drives would help break a downward cycle of ever-increasing and environmentally damaging pesticide over-use,” said Annabel Guichard, the paper’s first author.

The researchers describe two versions of the allelic drive, including “copy-cutting,” in which researchers use the CRISPR system to selectively cut the undesired version of a gene, and a more broadly applicable version referred to as “copy-grafting” that promotes transmission of a favored allele next to the site that is selectively protected from gRNA cleavage.

“An unexpected finding from this study is that mistakes created by such allelic drives do not get transmitted to the next generation,” said Guichard. “These mutations instead produce an unusual form of lethality referred to as ‘lethal mosaicism.’ This process helps make allelic drives more efficient by immediately eliminating unwanted mutations created by CRISPR-based drives.”

Although demonstrated in fruit flies, the new technology also has potential for broad application in insects, mammals and plants. According to the researchers, several variations of the allelic drive technology could be developed with combinations of favorable traits in crops that, for example, thrive in poor soil and arid environments to help feed the ever-growing world population.

Beyond environmental applications, allelic drives should enable next-generation engineering of animal models to study human disease as well as answer important questions in basic science. As a member of the Tata Institute for Genetics and Society (TIGS), Bier says allelic drives could be used to aid in environmental conservation efforts to protect vulnerable endemic species or stop the spread of invasive species.

Gene drives and active genetics systems are now being developed for use in mammals. The scientists say allelic drives could accelerate new laboratory strains of animal models of human disease that aid in the development of new cures.

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

Efficient allelic-drive in Drosophila by Annabel Guichard, Tisha Haque, Marketta Bobik, Xiang-Ru S. Xu, Carissa Klanseck, Raja Babu Singh Kushwah, Mateus Berni, Bhagyashree Kaduskar, Valentino M. Gantz & Ethan Bier. Nature Communicationsvolume 10, Article number: 1640 (2019) DOI: https://doi.org/10.1038/s41467-019-09694-w Published 09 April 2019

This paper is open access.

For anyone new to gene drives, I have a February 8, 2018 posting that highlights a report from the UK on the latest in genetic engineering, which provides a definition for [synthetic] gene drives, and if you scroll down about 75% of the way, you’ll also find excerpts from an article for The Atlantic by Ed Yong on gene drives as proposed for a project in New Zealand.

Controlling agricultural pests with CRISPR-based technology

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

Flies carry nanoparticles; EPA invites comments; scientific collaboration in virtual worlds

A new study is suggesting that flies exposed to nanoparticles in manufacturing areas or other places with heavy concentrations could accumulate the particles on their bodies and transport them elsewhere. From the media release on Nanowerk News,

During the experiments, the researchers noted that contaminated flies transferred nanoparticles to other flies, and realized that such transfer could also occur between flies and humans in the future. The transfer involved very low levels of nanoparticles, which did not have adverse effects on the fruit flies.

It makes perfect sense when you think about it. Flies pick up and transport all manner of entities so why wouldn’t they pick up nanoparticles in their vicinity?

In other news, the US Environmental Protection Agency (EPA) has asked for comments on case studies of nanoscale titanium dioxide in water treatment and sunscreens. Presumably you have to be a US citizen to participate. For more information on the call for comments, check out this item on Nanowerk News. From the item,

EPA is announcing a 45-day public comment period for the draft document, Nanomaterial Case Studies: Nanoscale Titanium Dioxide in Water Treatment and Topical Sunscreen (External Review Draft), as announced in the July 31, 2009 Federal Register Notice. The deadline for comments is September 14, 2009.

Yesterday, I came across an announcement about scientific collaboration in a virtual world (specifically Second Life). It’s the first professional scientific organization, Meta Institute for Computational Astrophysics (MICA), based entirely in a virtual world.

This idea contrasts somewhat with the NanoLands concept from the National Physical Laboratory in the UK where an organization with a physical location creates a virtual location. (You can see my interview with Troy McConaghy, part of the original NanoLands design team, here.)  The project blog seems to have been newly revived and you can find out more about NanoLands and their latest machinima movies. (If you want to see the machinima, you need a Second Life account.)

What I found particularly interesting about MICA is this bit from their media release on Physorg.com,

In addition to getting people together in a free and convenient way, virtual worlds can offer new possibilities for scientific visualization or “visual analytics.” As data sets become larger and more complex, visualization can help researchers better understand different phenomena. Virtual worlds not only offer visualization, but also enable researchers to become immersed in data and simulations, which may help scientists think differently about data and patterns. Multi-dimensional data visualization can provide further advantages for certain types of data. The researchers found that they can encode data in spaces with up to 12 dimensions, although they run into the challenge of getting the human mind to easily grasp the encoded content.

Shades of multimodal discourse! More tomorrow.