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Decoding Living Systems: from cell to ecosystem

At Earlham Institute, we task ourselves with “decoding living systems”. How does an open, multidisciplinary approach combining NGS, supercomputing, synthetic biology & bioinformatics help us to tell the most fascinating story of all?

March 28, 2018

At Earlham Institute, we task ourselves with “decoding living systems”.

Using powerful computational tools, along with the latest next generation genome sequencing equipment, from synthetic biology to multiscale modelling approaches, we are piecing together the jigsaw of how life is written, how evolution has shaped it, and how living things have inextricably intertwined over hundreds of millions of years to produce all of life’s dazzling diversity.

How does an open, multidisciplinary approach help us to tell the most fascinating story of all?

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How does an open, multidisciplinary approach help us to tell the most fascinating story of all?

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The cell.

You could argue for a lifetime about what qualifies the label of “life” or “living.” For the sake of simplicity, let’s begin with the cell.

The cell is the basic unit of life as we know it and is how we picture the gradual evolution of living things along a many-branched family tree, beginning with the last universal common ancestor (LUCA) of every single- or multi-celled creature on earth and ending only when our watery rock is consumed as the sun balloons into a red giant, an event which even the tardigrades might struggle to cope with.

That is, unless humans or any of the other species on earth manage to colonise another solar system. In that case, our tree of life will carry on expanding long into the future, somewhere in a galaxy far, far away.

However, modelling the future is the remit of climate scientists, meteorologists and economists.

Understanding life on earth, how it came to be, how it has been shaped over hundreds of millions of years of evolution, and how knowledge of this means that we can rebuild it from its very basic building blocks is where institutes such as EI come in.

By staying at the very cusp of advances in the life sciences, armed with a cutting edge toolkit of next generation genome sequencing platforms, high performance computational resources, along with talented programmers, bioinformaticians and other scientists with very diverse skills, we are in a great position to harness the advances of the present to discover the stories of the past in order to have a positive impact for the future.

Cells come in many shapes and sizes. Here are some unicellular green algae up close, as seen through a microscope. Credit: Ye.Maltsev, Shutterstock

Algae cells

Evolution.

As with cells, science as a field has witnessed vast evolution since its beginnings rooted in the philosophy and philosophers of the ancient world.

And, like the Cambrian explosion that saw complex multicellular life erupt from the seas and oceans, scientific evolution has accelerated swiftly into various revolutions, aided in the most part by a concomitant explosion in technological discovery and capacity over the last few centuries in particular.

Thus, today, less than 400 years after Robert Hooke discovered the cell, while Newton was busy discovering gravity, we have hurtled through a new world of biological innovation that started slowly but gained pace, along with the technology that came along with it.

Robert Hooke saw the first cells through one of the first microscopes (admittedly unwittingly), which have since become powerful enough that we can visualise mere molecules using beams of electrons, while Newton’s observations on light have become such that we can visualise chemical reactions inside cells in real time using coloured lasers (and Earlham Institute sequenced Newton’s apple tree not so long ago).

Those first microscopes remained almost unchanged for another couple of hundred years, yet at this point discovery truly started accelerating when Carl Zeiss (the company Zeiss founded is still going very strong today) hired Otto Schott (the inventor of borosilicate glass) and Ernst Abbe (who was one of the forerunners of modern social legislation, such as the eight hour work day).

What is poignant is that this was around the same time that Louis Pasteur was successfully vaccinating people against viruses such as rabies, developing his germ theory of disease and destroying the idea of spontaneous generation. In the UK, Charles Darwin was busy piecing together his groundbreaking and revolutionary work on the Origin of Species.

Meanwhile, Charles Babbage and Ada Lovelace were setting us on the road to computers and computer programming with their pioneering Analytical Engine, which inspired the way to the Manchester Mark 1 running the first ever computer program a century later.

For a long time, subjects such as chemistry, biology, physics, computing and more have been seen as differing subjects with distinct paths. Pasteur himself had to avoid dismissiveness over his initial discoveries due to his being trained as a chemist.

Today, in institutes such as EI, these diverse disciplines have coalesced, advancing each and every field in the process. When once it took years to sequence a gene using manual methods (only decades ago), we can now run entire strands of DNA through a handheld Oxford Nanopore MinION and convert the signal into a genome sequence within hours on a computer.

We can use powerful microscopes to identify single cells, then load these into machines that can sequence their genomes individually. We can use robots and drones to image crops in fields, then use algorithms and machine learning to teach computers how to spot the differences due to disease, weather or a genetic change. We can program machines to write DNA molecules from scratch, then stitch them together to be able to make proteins that can manufacture medicines in a test tube.

Computing, biology, chemistry, physics and engineering are all as inextricably linked in unravelling the complexities of life as the intricately woven webs of life which we are trying to unravel.

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Computing, biology, chemistry, physics and engineering are all as inextricably linked in unravelling the complexities of life as the intricately woven webs of life which we are trying to unravel.

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Open science.

Where do we start?

There’s probably not a correct answer, but armed with a suite of next generation sequencing (NGS) tools, we are now at the stage when we can sequence a complex genome in less than a week for next to nothing.

However, an Illumia HiSeq pipeline can produce more data in one week than the average computer knows what to do with, and stitching together a genome is like trying to embroider a night sky using 50 shades of grey thread.

This is where supercomputers come in, along with bioinformaticians who write algorithms that help make sense of the data that comes out of sequencing machines. Most of the software & tools developed at EI (from KAT to Portcullis and Mikado) are open source, and increasingly available to everyone through platforms such as Cyverse UK and Galaxy.

A biohacker in his or her apartment in New York can purchase a MinION for £1000 and perform up to 12 runs on just about any piece of DNA he or she wants a genome sequence for and, using open source tools such as NanoOK, can have a decent stab at piecing together that genome with a fair degree of accuracy.

Yet, de novo whole genome sequencing is just a part of the picture.

While sequencing and bioinformatics research at EI has contributed to each and every release of the global effort on completing the wheat genome, including the two latest, most up to date versions, the applications of our multidisciplinary research extend far beyond knowing the As, Gs, Cs and Ts of DNA.

Using platforms such as the PacBio, teams have been able to explore the genetic diversity within the R genes that allow the wild relatives of our crop plants to defend themselves against disease-causing pathogens. Using phylogenetics, tied with super-fast computational resources, we can identify how these genes mix and match parts in order to keep up with an ever-evolving pestilent threat.

Not limited to crops and their pathogens, bioinformatics and NGS can be applied to study pests such as the green peach aphid, and how they are so able to adapt to a range of host species.

Not limited to the study of food plants, our scientists have been at the forefront into research investigating threats to our economy and ecosystems, such as the ash dieback epidemic of European ash trees, or the varroa mite threat to bees.

Not limited to plant biology, our bioinformaticians look at all domains of life: the salmonella that infects a human gut, the rust that sweeps through a crop of wheat, the aphids that rampage through a range of crops, the algae that bloom in the frosty Antarctic, the ash trees trying to resist an epidemic, the cichlid fish that brighten the African great lakes, hardy desert mice, chlamydia-ridden koalas, pink pigeons on the brink of extinction and hundreds more.

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Importantly, this research is helping to answer globally important questions, spanning biodiversity, health, farming, food security and the bioeconomy; all through fostering a multidisciplinary symbiosis in the life sciences.

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Credit: Quick Shot/Shutterstock.com

Multidisciplinary research with global importance.

The combination of resources and expertise at Earlham Institute allows us to decode living systems at each and every stage: from the single cell sequencing of life’s basic units, through to the interactions that occur within and between organisms ranging from cells through to entire ecosystems.

Embracing NGS and synthetic biology in the wet lab through to developing tools and algorithms in the dry lab, pursuing robotics, machine learning, artificial intelligence and breakthroughs in high performance computing, as well as putting open data out to open access, makes EI a truly 21st century institute in which to perform leading scientific research.

Importantly, this research is helping to answer globally important questions, spanning biodiversity, health, farming, food security and the bioeconomy; all through fostering a multidisciplinary symbiosis in the life sciences.

Article author

Peter Bickerton

Scientific Communications & Outreach Manager

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