The Blocksford Brickopore LEGO sequencer highlights how we can engage both the public and scientists alike with science communication and outreach.
Jim Lipscombe, an automation specialist at the Earlham Institute, loves getting stuck in to public engagement. An enthusiastic communicator of science and a master LEGO® constructor (previous designs include a centrifuge), Jim fills us in on the success of Earlham Institute’s first LEGO® sequencer - the Blocksford Brickopore.
The Earlham Institute (EI) showcased its work at the 2018 Norwich Science Festival with two interactive stands. One stand was devoted to its efforts to save the endangered Pink Pigeon (Nesoenas mayeri) of Mauritius from extinction due to a genetic bottleneck (among several other factors such as habitat destruction and introduced pests); and another devoted to the business of sequencing DNA.
Scientists from EI performed a live sequencing of the “NedOme” – the genome of PhD student Ned Peel (Homo sapiens) utilising the Oxford Nanopore MinION™ portable sequencer.
EI also presented its LEGO® DNA sequencer – the Blocksford Brickopore – to the public for the first time. With the recent announcement that Illumina will acquire Pacific Biosciences, Iain Macaulay and Richard Leggett’s creation is a timely addition to a market in need of more competition.
Children, big and small, love LEGO® and its use as a science communication tool has an ever-growing pool of enthusiasts at EI and beyond (check out Monster Lab, for one). The success of EI’s LEGO® sequencer shows why the humble brainchild of a Jutlandian carpenter is so effective. Imagination.
The sequencer is designed to determine the order of red (“T”), green (“A”), yellow (“G”) and blue (“C”) LEGO bricks arranged in a stack of twenty-two with a few white bricks added to one end. In the laboratory, a DNA molecule prepared for real sequencing is referred to as a library and will often have some kind of adapter added on to make it manipulatable.
In this case the white blocks calibrate the sequencer so that it starts to read the sequence at the right position.
The children at the Science Festival were asked to make their own sequencing library with the order of DNA letters limited only by their imagination – there are nearly 1.8x1013 permutations of 22 nucleotides. The “libraries” that the children produced were a blend of randomness and order.
Although DNA sequence is not random in real genomes, to the untrained eye much of it would appear so. Patterns appear almost wherever we look in nature and genomes are no exception – long stretches of a single nucleotide or repeated motifs have been the bane of many a sequencer and bioinformatician over the years.
The LEGO® libraries were placed in the instrument and fed past a device that measures the intensity of reflected light so that each brick could be identified by its colour. The order of bricks was then returned as a DNA sequence and compared to a database of known sequences using an algorithm called BLAST (Basic Local Alignment Search Tool).
This is where the imagination of children really got fired up! Every child was excited to find out if their made-up DNA sequence was a match for their favourite animal or plant.
Is it a cat, a bumble bee, a daisy, a unicorn? Of course, a 22nt DNA sequence is extremely likely to be non-exclusive and indeed every sequence was at least a 99% match to multiple organisms.
The variety of organisms returned by the BLAST output covered almost the entire tree of life – there were representatives of many of the major taxonomic classes. Many were species familiar to Norwich’s plethora of biologists - wheat, human, brassica, mouse, Arabidopsis thaliana – but many were less well known or understood.
The children were delighted to have made a DNA sequence that was a match for something cute and fluffy such as the Common Degu (Octodon degus) or for a parasitic worm (Haemonchus contortus) that feeds on the blood of sheep and goats.
One boy went away delighted that the top match for his sequence was an Alligator – his favourite animal. A girl of about seven years old told me all about the importance of the Honey Bee (Apis mellifera) to which her DNA sequence matched best, and how she loved honey on her toast.
Whilst nearly all the children understood that differences in our DNA can be responsible for differences between us, almost all the children were surprised to learn just how similar we are to one another and to some quite different organisms.
Communicating science to children is always fun and often surprising - but one BLAST result really hit us between the eyes… at least at first. A hypothetical protein belonging to Ceraceosorus guamensis - a smut fungi only recently described - appeared top of the BLAST output from a very excitable young visitor to the stand.
Not recognising the Latin name, I searched the internet, completely overlooking the words at the top of my tiny phone screen:
The child was unsurprisingly amazed but did not stick around long enough to find out the truth. Hopefully, her imagination will have been stimulated enough for her to find out about the reality of sequencing Jurassic DNA and maybe even about the intriguing and mind-bogglingly varied kingdom of the fungi.
One of the great lessons that science can teach is that being right is often a temporary arrangement and that taking things at face value can be a fool’s game. Engaging children from an early age in the possibilities, however unlikely, of science and technology is, I believe, a critical step on the path to them becoming scientists. And the world really needs more scientists.
