Tag Archives: DNA

reverse ageing

Is it possible to reverse ageing?

Featured image above: reverse ageing.

Since successful genome sequencing was first announced in 2000 by geneticists Craig Venter and Francis Collins, the cost of mapping DNA’s roughly three billion base pairs has fallen exponentially. Venter’s effort to sequence his genome cost a reported US$100 million and took nine months. In March, Veritas Genetics announced pre-orders for whole genome sequencing, plus interpretation and counselling, for US$999.

Another genetics-based start-up, Human Longevity Inc (HLI), believes abundant, relatively affordable sequencing and collecting other biological data will revolutionise healthcare delivery. Founded by Venter, stem cell specialist Robert Hariri and entrepreneur Peter Diamandis, it claims to have sequenced more human genomes than the rest of the world combined, with 20,000 last year, a goal of reaching 100,000 this year and over a million by 2020.

HLI offers to “fully digitise” a patient’s body – including genotypic and phenotypic data collection, and MRI, brain vascular system scans – under its US$25,000 Health Nucleus service. Large-scale machine learning is applied to genomes and phenotypic data, following the efforts at what Venter has called “digitising biology”.

The claim is that artificial intelligence (AI) can predict maladies before they emerge, with “many” successes in saving lives seen in the first year alone. The company’s business includes an FDA-approved stem cell therapy line and individualised medicines. The slogan “make 100 the new 60” is sometimes mentioned in interviews with founders. Their optimism is not isolated. Venture capitalist Peter Thiel admits he takes human growth hormone to maintain muscle mass, confident the heightened risk of cancer will be dealt with completely by a cancer cure, and plans to live to 120.

“We understand what the surgeon needs and we embed that in an algorithm so it’s full automated.”

Bill Maris, CEO of GV (formerly Google Ventures), provocatively said last year that he thinks it’s possible to live to 500. An anit-ageing crusader, biological gerontologist Dr Aubrey de Grey, co-founder and chief science officer of Strategies for Engineered Negligible Senescence (SENS, whose backers include Thiel), has claimed that people alive today might live to 1000.

Longevity expectations are constantly being updated. Consider that, in 1928, American demographer Louis Dublin put the upper limit of the average human lifespan at 64.8. How long a life might possibly last is a complex topic and there’s “some debate”, says Professor of Actuarial Studies at UNSW Michael Sherris.

He says there have been studies examining how long a life could be extended if certain types of mortality, such as cancer, were eliminated, points out Sherris.

“However, humans will still die of something else,” he adds. “The reality is that the oldest person lived to 122.”

Will we see a 1000-year-old human? It isn’t known. What is clear, though, is that efforts to extend health and improve lives have gotten increasingly sophisticated.

The definition of bioengineering has also grown and changed over the years. Now concerning fields including biomaterials, bioinformatics and computational biology, it has expanded with the ability to apply engineering principles at the cellular and molecular level.

Reverse ageing
A team led by Professor Jason Cooper-White at the University of Queensland’s Australian Institute for Biotechnology and Nanotechnology (AIBN) recently published research showing a novel stem cell screening method, a “lab on a chip”, almost. The credit card-sized device looks a boon for productivity. According to AIBN, it is able to run “8,100 experiments at one time”, deliver a five- to ten-fold increase in stem cell differentiation, and decrease the cost of this by 100 to 1,000 by reducing cell media culture used. The Cooper-White Lab focusses on “cardiac and vascular development, disease and regeneration”. Among many awards, Professor Cooper-White last year picked up the Aon Risk Solutions Regenerative Medicine Award. Credit: AIBN

Editing out problems to reverse ageing

What if, further than reading and comprehending the code life is written in, it could also be rewritten as desired? A technique enabling this with better productivity and accuracy than any before it, has gotten many excited about this possibility.

“In terms of speed, it’s probably 10 times as quick as the old technology and is five to 10 times as cheap,” says Professor Robert Brink, Chief Scientist at the Garvan Institute of Medical Research’s MEGA Genome Engineering Facility.

The facility uses the CRISPR/Cas9 process to make genetically-engineered mice for academic and research institute clients. Like many labs, Brink’s facility has embraced CRISPR/Cas9, which has made editing plant and animal DNA so accessible even amateurs are dabbling.

First described in a June 2012 paper in Science, CRISPR/Cas9 is an adaptation of bacteria’s defences against viruses. Using a guide RNA matching a target’s DNA, the Cas9 in the title is an endonuclease that makes a precise cut at the site matching the RNA guide. Used against a virus, the cut degrades and kills it. The triumphant bacteria cell then keeps a piece of viral DNA for later use and identification (described sometimes as like an immunisation card). This is assimilated at a locus in a chromosome known as CRISPR (short for clustered regularly spaced short palindromic repeats).

In DNA more complicated than a virus’s, the cut DNA is able to repair itself, and incorporates specific bits of the new material into its sequence before joining the cut back up. Though ‘off-target’ gene edits are an issue being addressed, the technique has grabbed lots of attention. Some claim it could earn a Nobel prize this year. There is hope it can be used to eventually address gene disorders, such as Beta thalassemias and Huntington’s disease.

“Probably the obvious ones are gene therapy, for humans, and agricultural applications in plants and animals,” says Dr George Church of Harvard Medical School.

Among numerous appointments, Church is Professor of Genetics at Harvard Medical School and founding core faculty member at the Wyss Institute for Biologically Inspired Engineering. Last year, a team led by Dr Church used CRISPR to remove one of the major barriers to pig-human organ transplants – retroviral DNA – in pig embryos.

You can have what are called, ‘universal donors’. That’s being used, for example, in making cells that fight cancer.

“We’re now at the point where it used to be that you would have to have a perfect match between donor and recipient of human cells, but that was because you couldn’t engineer either one of them genetically,” he says. “You can engineer the donor so that it doesn’t cause an immune reaction. Now, you can have what are called, ‘universal donors’. That’s being used, for example, in making T cells that fight cancer – what some of us call CAR-T cells. You can use CRISPR to engineer them so that they’re not only effective against your cancer, but they don’t cause immune complications.”

Uncertainty exists in a number of areas regarding CRISPR (including patent disputes, as well as ethical concerns). However, there is no doubt it has promise.

“I think it will eventually have a great impact on medicine,” believes Brink. “It’s come so far, so quickly already that it’s almost hard to predict… Being able to do things and also being able to ensure everyone it’s safe is another thing, but that will happen.”

And as far as acceptance by the general public? Everything that works to overcome nature seems, well, unnatural, at least at first. Then it’s easier to accept once the benefits of are apparent. Church – who believes we could reverse ageing in five or six years – is hopeful about the future. He also feels the world needs people leery about progress, and who might even throw up a “playing God” argument or two.

“I mean it’s good to have people who don’t drive cars and don’t wear clothes and things like that, [and] it’s good to have people who are anti-technology because they give us an alternative way of thinking about things,” he says.

“[Genetic modification] is now broadly accepted in the sense that in many countries people eat genetically-modified foods and almost all countries, they use genetically-modified bacteria to make drugs like Insulin. I think there are very few people who would refuse to take Insulin just because it’s made in bacteria.”

Reverse ageing
The Australian Centre of Excellence in Electromaterials Science (ACES) at the University of Wollongong, is a leader in biological 3D printing. Alongside three other universities, it offers the world’s first masters degree in biofabrication. The highly-interdisciplinary role of biofabricator “melds technical skills in materials, mechatronics and biology with the clinical sciences” says ACES Director, Professor Gordon Wallace. One of its projects is “layered brain-like structures”. Using layered bio-ink made of carbohydrates and neurons, the work adds to progress on a “bench-top brain”. Such a brain would be hugely useful for new drugs and electroceuticals. Professor Wallace, recently in the news for the BioPen stem cell printer, believes, in the coming years and with regulatory approval, cartilage for preventing arthritis, islet cells to treat diabetes, and stem cells will all be biofabricated treatments. Credit: ACES

A complete mindshift

Extended, healthier lives are all well and good. However, humans are constrained by the upper limits of what our cells are capable of, believes Dr Randal Koene.

For that and other reasons, the Dutch neuroscientist and founder of Carbon Copies is advancing the goal of Substrate Independent Minds (SIM). The most conservative form (relatively speaking) of SIM is Whole Brain Emulation, a reverse-engineering of our grey matter.

“In system identification, you pick something as your black box, a piece of the puzzle small enough to describe by using the information you can glean about signals going in and signals going out,” he explains, adding that the approach is that of mainstream neuroscience. “The system identification approach is used in neuroscience explicitly both in brain-machine interfaces, and in the work on prostheses.”

No brain much more complicated than a roundworm’s has been emulated yet. Its 302 neurons are a fraction of the human brain’s roughly 100 billion.

Koene believes that a drosophila fly, with a connectome of 100,000 or so neurons, could be emulated within the next decade. He is reluctant to predict when this might be achieved for people.

There’s reason for hope, though, with research at University of Southern California’s Center for Neural Engineering pointing the way.

 “The people from the [Theodore] Berger lab at USC, they’ve had some really good results using the system identification approach to make a neural prosthesis,” Koene says.

Koene counts being able to replace the function of part of a brain as the “smallest precursor” to whole brain emulation, with the end goal a mind that can operate without a body.

reverse ageing
Professor Milan Brandt, Technical Director of RMIT’s $25 million Advanced Manufacturing Precinct, has led the university in numerous collaborative projects. These include an Australian-first 3D printed spinal replacement with Anatomics, a vertebral cage for a patient with a deformity and excruciating back pain.  Other endeavours include the university’s provisionally patented Just-In-Time patient-specific bone implant method. To be useful away from its creators, the process – which creates implants with lattice-like mesh structures that emulate the weight and flex of bone – needs to be usable by surgeons with no prior experience with 3D printing. “We understand what the surgeon needs and we embed that in an algorithm so that it’s fully automated,” Dr Martin Leary tells create. Credit: RMIT

 – Simon Lawrence

This article was originally published in the July 2016 issue of create – Engineers Australia‘s member magazine. Read the original article here.

directed evolution

First woman wins Millenium Technology Prize

Featured image above: Frances Arnold. Credit: Caltech

Frances Arnold, the Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry at the California Institute of Technology (Caltech), has been awarded the Millennium Technology Prize for her “directed evolution” method, which creates new and better proteins in the laboratory using principles of evolution. The Millennium Technology Prize, worth one million euros (approximately A$1.5 million), is the world’s most prominent award for technological innovations that enhance the quality of people’s lives.

Directed evolution, first pioneered in the early 1990s, is a key factor in green technologies for a wide range of products, from biofuels to pharmaceuticals, agricultural chemicals, paper products, and more.

The technique enlists the help of nature’s design process — evolution — to come up with better enzymes, which are molecules that catalyse, or facilitate, chemical reactions. In the same way that breeders mate cats or dogs to bring out desired traits, scientists use directed evolution to create desired enzymes.

“We can do what nature takes millions of years to do in a matter of weeks,” says Arnold, who is also director of the Donna and Benjamin M. Rosen Bioengineering Centre at Caltech. “The most beautiful, complex, and functional objects on the planet have been made by evolution. We can now use evolution to make things that no human knows how to design. Evolution is the most powerful engineering method in the world, and we should make use of it to find new biological solutions to problems.”

Directed evolution works by inducing mutations to the DNA, or gene, that encodes a particular enzyme. An array of thousands of mutated enzymes is produced, and then tested for a desired trait. The top-performing enzymes are selected and the process is repeated to further enhance the enzyme’s performance. For instance, in 2009, Arnold and her team engineered enzymes that break down cellulose, the main component of plant-cell walls, creating better catalysts for turning agricultural wastes into fuels and chemicals.

“It’s redesign by evolution,” says Arnold. “This method can be used to improve any enzyme, and make it do something new it doesn’t do in nature.”

Today, directed evolution is at work in hundreds of laboratories and companies that make everything from laundry detergent to medicines, including a drug for treating type 2 diabetes. Enzymes created using the technique have replaced toxic chemicals in many industrial processes.

“My entire career I have been concerned about the damage we are doing to the planet and each other,” says Arnold. “Science and technology can play a major role in mitigating our negative influences on the environment. Changing behavior is even more important. However, I feel that change is easier when there are good, economically viable alternatives to harmful habits.”

“Frances is a distinguished engineer, a pioneering researcher, a great role model for young men and women, and a successful entrepreneur who has had a profound impact on the way we think about protein engineering and the biotechnology industry,” says David Tirrell, the Ross McCollum-William H. Corcoran Professor of Chemistry and Chemical Engineering at Caltech. “The Millenium Technology Prize provides wonderful recognition of her extraordinary contributions to science, technology, and society.”

Arnold received her undergraduate degree in mechanical and aerospace engineering at Princeton University in 1979. She earned her graduate degree in chemical engineering from UC Berkeley in 1985. She arrived at Caltech as a visiting associate in 1986 and became an assistant professor in 1987, associate professor in 1992, professor in 1996, and Dickinson Professor in 2000.

She is the recipient of numerous awards, including in 2011 both the Charles Stark Draper Prize, the engineering profession’s highest honor, and the National Medal of Technology and Innovation. Arnold is one of a very small number of individuals to be elected to all three branches of the National Academies—the National Academy of Engineering (2000), the Institute of Medicine (2004), and the National Academy of Sciences (2008)—and the first woman elected to all three branches.

“I certainly hope that young women can see themselves in my position someday. I hope that my getting this prize will highlight the fact that yes, women can do this, they can do it well, and that they can make a contribution to the world and be recognised for it,” says Arnold.

The Millennium Technology Prize is awarded every two years by Technology Academy Finland (TAF) to “groundbreaking technological innovations that enhance the quality of people’s lives in a sustainable manner,” according to the prize website. The prize was first awarded in 2004. Past recipients include Sir Tim Berners-Lee, creator of the World Wide Web; Shuji Nakamura, the inventor of bright blue and white LEDs; and ethical stem cell pioneer Shinya Yamanaka. Arnold is the first woman to win the prize.

– Whitney Clavin

This article was first published by Caltech on 24 May 2016. Read the original article here.

Protecting Australian wine

Protecting Australian wine

Featured image above: Plant Biosecurity Cooperative Research Centre

Phylloxera is an aphid-like insect that is a pest of commercial grapevines worldwide. The Plant Biosecurity Cooperative Research Centre (PBCRC) is funding a project led by Vinehealth Australia to conduct field trials for a new, accurate, sensitive and cost-effective DNA-based test for detecting the pest.

CEO of Vinehealth Australia, Alan Nankivell, who is leading the project, says phylloxera had a significant economic impact on the wine industry, as “the quality of our wines is based on the quality of our vines”. Eighty per cent of Australia’s vineyards have vines that are own-rooted, rather than grafted onto resistant rootstock; some are very old and the wines produced from these are highly sought after.

Phylloxera (Daktulosphaira vitifoliae) feeds on grapevine roots and leaves them open to bacterial infection, which can result in rot and necrotic death due to cell injury. It destroyed substantial areas of vines in France in the mid-19th century and has affected several winegrowing areas of Australia; the only effective treatment is removing infested vines and replanting with resistant rootstock.

Financially, the cost of managing a vineyard with phylloxera is estimated to range from 10–20% in additional operating costs.

The current method of detection uses a shovel and magnifying glass to inspect sites in areas of low vigour; however, phylloxera may have been present for some time and the test is usually conducted in summer, one of the industry’s busiest seasons.

The new DNA-based test requires 10-cm soil core samples to be taken 5 cm from the vine’s trunk. The samples are then sealed and sent to a lab where they are dried and tested for the presence of phylloxera DNA.

Protecting Australian wine
Alan Nankivell, CEO of Vinehealth Australia, is leading research to develop a new test for phylloxera of grapevines. Photo credit: PBCRC

Nankivell says the incidence of finding phylloxera using the test was very high (around 98%), even when the amounts of phylloxera present were low.

“At the moment, we’re able to find phylloxera at sites any time of the year.”

The new DNA-based test could help prevent the spread of phylloxera in Australia, as those who have it on their property can determine where it is and whether it is spreading.

Sampling in vineyards across Australia over time will establish a baseline for the maintenance of area freedom. Nankivell says with this baseline in place, the quarantine management and farm-gate hygiene of vineyards will improve industry knowledge about where phylloxera is and isn’t.

PBCRC researchers are currently working to establish the most suitable grid pattern for taking the soil core samples.

They will also compare the DNA sample method with two other methods: the ‘shovel method’ and another using emergence traps to catch insects inside an inverted container placed on the soil, to determine performance against selected criteria.

This research strongly supports the wine industry’s focus on identifying and managing biosecurity threats to ensure the ongoing health of grapevines. Healthy vines are the foundation for a prosperous Australian wine industry.

–Laura Boness

To learn more about phylloxera, click here or watch this video about the Phylloxera Rezoning Project carried out in Australia:

Doorway to cancer data

Precision medicine is opening the doorway to cancer data and offering hope to cancer patients. The power of genomics and the masses of data it creates is transforming cancer research and allowing personalised treatments with more proven effects.

Like hundreds of other cancer researchers, Mark Ragan and his team at The University of Queensland’s Institute for Molecular Bioscience (IMB) need to design experiments based on data from human and cancer genetics. Using data chips and next generation sequencing they must assemble their genetic data, interpret it to understand what genes their data refer to by comparison with other samples, and then classify patients’ cancer into subtypes. If they can’t match to an existing subtype, they identify a new one. Ragan says this intensive work requires access to as much genetic data as possible.

“It would literally be impossible without the data reuse that TCGA and other genome research programs offer”

Doorway to cancer data

Luckily, there are portals with this type of data. One of the first to start collecting cancer genome data was the The Cancer Genome Atlas (TCGA). The initials TCGA also make up the four-letter code of nucleotide bases thymine, cytosine, guanine and adenine that DNA uses to ‘write’ genetic information.

Doorway to cancer data
Photo by Richard Ricciardi.

TCGA was started by the US National Institutes of Health (specifically the National Cancer Institute and the National Human Genome Research Institute) in 2006. Ragan says its initial goal was to generate data from researchers across research institutions on two cancer types. Early success expanded the initial goal to collect and profile more than 10,000 samples from over 20 tumour types. While the sample collection phase ended in 2013, data reuse ensures the data generated from those samples are still being analysed. Over 2700 papers have been published by TCGA data so far, including Australian researchers.

The data portal for the TCGA is “amazing” says Ragan. “It’s a really powerful portal that lets you ask questions and interrogate gigantic amounts of cancer genome data, including sequences, survival rates and subtype classifications.”

“Just about everything in it is open access, and the raw data, which isn’t open access, is made available by applying through research institutions’ ethics committees.”

A newer initiative inspired by the success of TCGA, the International Cancer Genome Consortium (ICGC), is an international project in which Ragan’s colleagues play a part. ICGC is built on the TCGA project, which provides about 60% of the patient data in ICGC’s Data Coordination Center. ICGC aims to cover 50 tumour types and currently funds 78 international cancer genome projects like the Australian project at IMB.

“Our research into breast cancer subtypes and survival would literally be impossible without the data reuse that TCGA and other genome research programs offer. We can tell if we’ve discovered a new cancer subtype or not, or even whether the existing data need reinterpreting,” says Ragan.

New treatments

Knowing a patient’s cancer subtype allows more tailored, evidence-based treatment, potentially increasing survival rates and quality of life by allowing clinicians to more confidently focus on prescribing the drugs most likely to succeed for a particular patient.

One of the exciting things Ragan and other researchers are finding from the data is that some quite different cancer types have a similar genetic basis. This means drugs to treat one type of cancer, such as breast cancer, could be used for another, such as ovarian cancer.

“Instead of waiting 10 years for a new drug to be developed, patients may be able to be treated straight away with a drug that’s already available for another cancer,” says Ragan.

That’s good news for patients, and it also makes drug development, which can cost hundreds of millions of dollars per drug, more cost-effective. This potentially creates a larger market for a given drug, and makes some drugs financially viable that otherwise wouldn’t get to market.

Story provided by Refraction Media.

Originally published in Share, the newsletter magazine of the Australian National Data Service (ANDS).

New tools in the fight against fish ferals

They’re known as the rabbits of Queensland’s rivers. Tilapia were introduced into Australia in the 1970s through the aquarium trade, and these African exotics are now one of the country’s most destructive pest fish.

“They’re like little bulldozers in a river,’’ says aquatic ecosystems biologist Dr Dean Gilligan. “They dig around in the bottom of rivers, pull out vegetation, stir up mud and generally trash the habitat for native species. They’re also bullies. They’re extremely aggressive toward native fish – and, unfortunately, can breed up into a very large biomass, just like carp.”

Gilligan is a senior fisheries research scientist with the NSW Department of Primary Industries, and leads the CRC’s inland water pests research program, whose focus is to develop new technologies to detect and better control pest fish.

With researchers at the University of Notre Dame in Illinois, US, scientists from the Queensland Department of Agriculture, Fisheries and Forestry and James Cook University have been working to develop a DNA surveillance technique to detect the presence of tilapia in creeks and other waterways.

The spread of tilapia has so far been confined to Queensland, where their range includes one of the state’s biggest river systems – the Burdekin. Several outbreaks in West Australian rivers near Geraldton were controlled thanks to early detection. Preventing the spread of the fish, particularly to the Murray-Darling Basin, is a key concern of the CRC.

Tilapia can thrive in polluted and degraded waterways, and are fast, prolific breeders. Several were added to an ornamental pond at a hotel golf course in Port Douglas, near Cairns. Two years later, an eradication program removed 16 tonnes of tilapia from the pond.

Gilligan says the DNA surveillance technique being developed by the Invasive Animals CRC will enable fisheries officers to more efficiently detect pest fish, even in low numbers.

“Instead of sending a whole team of people out with a boat, nets and a pile of equipment for several days, we can send one person, with a bucket, to collect around nine to 10 litres of water from a river,’’ Gilligan says.

“They dig around in the bottom of rivers, pull out vegetation, stir up mud and generally trash the habitat for native species. They’re also bullies.”

Dr Dean Gilligan leads the Invasive Animals CRC’s inland water pest program.
Dr Dean Gilligan leads the Invasive Animals CRC’s inland water pest program.

The water is filtered, using fine filter paper, and when filtration is complete, the paper is analysed using a standard polymerase chain reaction laboratory test to detect DNA fragments.

“It’s not instantaneous. It takes a couple of days to filter the water and run the test, but it’s a much faster, more reliable [method] of measuring pest fish incursions in a river than using nets, lines and boats. Once the test result is back, we can run a risk assessment and move on to developing an eradication program.”

The DNA surveillance technique was originally developed in the US to detect carp, which are now among Australia’s most destructive environmental pests. The CRC is also evaluating a naturally occurring virus found overseas as a biological control agent to reduce carp impact. Dr Ken McColl, a veterinary virologist at the CSIRO Australian Animal Health Laboratory in Geelong, is leading the research.

McColl is conducting tests to confirm the findings that this carp herpes virus is effective and that it is safe for release into Australia’s waterways to control carp without affecting humans or native species. If successful, the strategic control program will open up new areas of research.

“We’d see unprecedented massive fish kills of carp in rivers, so we need to look at ways to manage collection and disposal of thousands of dead carp,” says Gilligan. “Do they go to council tips as landfill, or could they be ploughed into paddocks as fertiliser? That’s all part of the challenge of developing an eradication technique.”

– Rosslyn Beeby