Tag Archives: neuroscience

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.

Using nanoparticles to transform glass

Featured image above: the making of a glass optical fibre

The innovative method was developed by researchers from The University of Adelaide in South Australia, which enables the glass to hold transparency and proceed into various shapes including very fine optical fibres.

Principal researcher Tim Zhao says this new method of injecting upconversion nanoparticles into glass could have multiple applications including remote nuclear radiation sensors, interactive 3D display screens and biomedical engineering equipment.

“For example, neuroscientists currently use dye injected into the brain and lasers to be able to guide a glass pipette to the site they are interested in,” he says.

“If fluorescent nanoparticles were embedded in the glass pipettes, the unique luminescence of the hybrid glass could act like a torch to guide the pipette directly to the individual neurons of interest.”

Upconversion nanoparticles are able to convert near infrared radiations with higher energy emissions or visible light.

They exhibit unique luminescent properties and show great potential for imaging and biodetection assays.

Zhao, a researcher at the University of Adelaide’s Institute for Photonics and Advanced Sensing (IPAS), says previous methods of integrating upconversion nanoparticles into glass did not allow researchers to have control over the nanoparticle properties, making it difficult to disperse.

“The key to our method was finding a balanced temperature. We heated the glass at a really high temperature, about 550-575°C, making it really homogenous to return its optical properties,” he says.

“After it was melted we lowered the temperature down as low as possible. Lowering the temperature makes it foam like water and then like honey at room temperature. At that point we enter in our nanoparticles and the glass helps it all disperse in time.”

Although the new method was developed with upconversion nanoparticles, researchers believe their new “direct-doping” approach can be generalised to other nanoparticles with interesting photonic, electronic and magnetic properties.

“We’ve seen remarkable progress in this area but the control over the nanoparticles and the glass compositions has been limited, restricting the development of many proposed applications,” says project leader Professor Heike Ebendorff-Heideprem.

“With our new direct doping method, which involves synthesising the nanoparticles and glass separately and then combining them using the right conditions, we’ve been able to keep the nanoparticles intact and well dispersed throughout the glass.

“We are heading towards a whole new world of hybrid glass and devices for light-based technologies.”

The research was conducted in collaboration with Macquarie University and University of Melbourne. It was published online in the journal Advanced Optical Materials.

– Caleb Radford

This article was first published by The Lead on 7 June 2016. Read the original article here.

Using algorithms to capture risk

IN THE HEALTH SECTOR, big data has been harnessed with remarkable success. One high-profile example is Google’s Flu Trends website, reported in a paper for the journal Nature in 2009 for accurately predicting the spread of epidemics based on the frequency of disease-related search queries.

Associate Professor Trish Williams, who heads the eHealth Research Group at Edith Cowan University in Joondalup, WA, says that unlike a lot of health research, projects using big data don’t focus on ‘cause and effect’. Instead, they tap into the huge potential of predictive analytics.

That’s an area where collaborative research can come to the fore, she says. Williams adds that big data research is most effective when done by cross-disciplinary teams who can both interpret information and present the findings to a broad audience.

“In health, it is really important that the semantics of the data are well-understood before you start analysing things,” she says. “You’ve also got to work out how to use some very big datasets, perhaps in ways that they weren’t necessarily intended to be used.”

“We’re working to improve the algorithms that detect what kind of problem the person has.”

This conundrum is very familiar to Associate Professor Jane Burns, CEO of the Young and Well CRC. When her team compared the results of a national survey that used ‘traditional’ computer-assisted telephone interviews with those from a similar Facebook survey, they expected both datasets would reveal similar trends.

“We found that the results were not similar at all; the internet results showed far higher levels of psychological distress,” she says, adding that there’s no sure way to work out which survey style had less bias. “Possibly, people are far more honest over the internet than they are over a telephone interview.”

Researching suicide indicators in social media is in its early stages, with researchers from the Young and Well CRC working with key industry partners such as Facebook, Twitter and Google.

“We’re trying to understand from a suicide prevention perspective, how we might be able to use big data to understand trends in the way in which people respond to things, to see if we can look to algorithms to capture some of the risks,” says Burns.

Twitter profile on Apple iPhone 5S
Social networking media holds a wealth of information on the public’s mental health.

With more than 500 million short messages going out through the Twitter network daily, Burns says that finding algorithms to uncover keywords for suicide risk is a huge challenge.

Included in the research is suicide contagion – where one suicidal act within a community increases the likelihood of more occurring. Burns says a key focus of their research around suicide contagion, as well as identifying early warning symptoms or signs, is initiating support networks.

Within the Young and Well CRC, Associate Professor Rafael Calvo of the University of Sydney is working to design tools that help moderators in online health-focused communities, such as youth mental health support service ReachOut.com, to provide appropriate feedback and support for their members.

Thousands of forum posts can be automatically processed, generating a report that prioritises more serious problems so moderators can respond immediately. The team has also developed suggested ‘intervention’ templates, which link to helpful resources.

“We have built the interface for the moderator, and we’re now working on improving the algorithms that detect what kind of problem the person has,” Calvo says.

One of the hopes for big data analysis is to uncover measurable biological indicators for devastating mental health disorders.
One of the hopes for big data analysis is to uncover measurable biological indicators for devastating mental health disorders.

Social media is just one of the big data examples in health. At the CRC for Mental Health, researchers are looking for biomarkers – measurable biological indicators that might enable early intervention for people at risk of Alzheimer’s disease, mood disorders, schizophrenia and Parkinson’s disease. Datasets include the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing, which has genomic information for more than 1500 people – some with normal cognitive function, others with mild cognitive impairment and others who have been diagnosed with Alzheimer’s disease.

Dr Noel Faux, a bioinformatician at the Florey Department of Neuroscience and Mental Health, says that the vast amounts of information already available include blood measurements of thousands of hormones and proteins. Cognitive and clinical assessments are also being gathered.

His team is working with software developer Arcitecta to help researchers capture clinical data on-site and feed it into a data repository that can be used by multiple research institutions.

www.youngandwellcrc.org.au
www.mentalhealthcrc.com
au.reachout.com

 

Tracking health

HealthTracks, a web-based tool built by the CRC for Spatial Information, has been used by researchers at Western Australia’s Department of Health to merge health data with spatially-based datasets. The aim is to identify populations at risk of disease and gaps in the location of essential health services.

So far, hospital and regional health data has been combined with public datasets via the WA Landgate Shared Land Information Platform. When rolled out nationally, the tool will include modular enhancements for the analysis of mental health, child health and environmental health data.

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