I have been irregular in my blog postings this year but, keeping in continuation to the best of biotech in 2013 and 2014, here is my list of the best of the breakthroughs in biotechnology this year. This list is subject to my attentional bias and in no particular order.
The most revolutionary of discoveries often disrupt dogmas held for years. This year was a year of firsts and saw many such dogmas being broken. The excitement around CRISPR-Cas 9, dubbed the biotech breakthrough of the century by MIT, continued to soar on with new applications and a new, better enzyme – Cfp1. Research in aging revived the dipping funding in degenerative disorders.
Proteins assembled by… other proteins
It has long been known that DNA is transcribed into mRNA, which contains the instructions for its translation into protein. Ribosomes mediate the assembly of proteins in the growing polypeptide chain and if anything goes wrong, quality control mechanisms stall the process. One of the proteins involved in quality control is Rqc2 and it instructs the ribosomes to add threonine and alanine amino acids in a random order to the partly made protein. It is still not clear whether this random sequence is a signal for destroying the partly made protein or a way to test if the ribosome functioning is proper.
Mitochondrial DNA moving between tumour cells
Turning the long –held belief that genes in higher organisms don’t move between cells (other than during reproduction), Malaghan Institute researchers observed mitochondrial gene transfer from normal tissue to melanoma cells, which had their mitochondrial DNA removed, in mice. It is likely that such gene transfer is a common mechanism during development. If that is true, it would greatly help in our understanding of over 200 diseases that can be attributed to defects in the mitochondrial DNA.
Genes that affect aging
In a study extending over ten years, researchers followed the growth of 4698 yeast (S. cerevisiae) strains, each with just a single gene knocked out. Removal of 238 genes was seen to significantly increase the lifespan of the yeast. Most of these genes are conserved in higher animals, including humans. All of these are potential targets to extend lifespan, but which of these can be altered is yet to be seen.
University of Bern researchers approached the same goal with another approach. They identified a single gene,azot, which is activated in less healthy cells and acts as a cell quality control mechanism in sensitive organs such as the brain or the gut. The researchers inserted a third copy of the gene and as a consequence the selection of the better cells was more efficient. The flies, thus, aged slower and were observed to live up to 60% longer than normal flies. Interestingly, the azot gene is conserved in humans and leads to the possibility of selecting better cells as an anti-aging mechanism.
Nanopore sequencing makes use of passing the DNA strand through a nanoscale hole. It has the dual benefits of long reads and generating large amounts of data, usually not seen together in other sequencing methodologies. A limitation is that the reads are much less accurate. The latest sequencer in the line, commercialized by Oxford Nanopore, is the size of a smartphone and can be connected to a laptop by USB. It is devices like these that would make sequencing far more accessible than it currently is.
The weirdest genome ever?
Tardigrades are known to survive in temperatures ranging from -272°C to 150°C, six times the pressure in the deepest ocean trenches, ionizing radiation, and even the vacuum of the outer space. The tardigrade genome was sequenced this year and turned out to be as strange as the organism itself. It has the most foreign DNA among all animals sequenced, amounting to roughly 1/6th of the genome. A later study, however, put the number of foreign genes at just around 500.
Editing human embryos
Editing the genome of human embryos was long anticipated, but became a reality in 2o15. Chinese researchers reported in April that they had tried to precisely alter a gene in every cell by using CRISPR-Cas9 system to modify non-viable human embryos. Of the 85 embryos experimented upon, only four had the targeted gene edited, but they too were riddled by genetic mosaics and DNA damage. The study raised questions on our understanding of genome editing and was followed by a lot of debate on its ethical considerations. Later in December, an international group of researchers called for a moratorium on making inheritable gene edits in the human genome until the risks have been properly assessed or there is a broad societal consensus on it.
Curing ‘incurable’ leukemia
TALENs, a gene editing technique preceding the CRISPR-Cas9 boom, were used to cure leukemia in a one-year old girl suffering from relapsed acute lymphoblastic leukemia. Healthy T-cells obtained from donors were modified by inserting new genes that armed them to specifically target leukemia cells. These modified cells were delivered intravenously, the girl was kept in isolation for a few months, and when it was confirmed that leukemia cells had been removed, a bone marrow transplant done to replenish the entire blood and immune system. If replicated, this approach can lead to cures for leukemia and cancer cells.
Biocompatible nanowire arrays were combined with select bacterial populations to a radical artificial photosynthesis system. The system captures carbon dioxide emissions and converts them into valuable products such as biodegradable plastics, drugs, and fuels. The solar-to-chemical conversion efficiency achieved was up to 0.38%, the same as that of a leaf. Once the efficiency would be greater than 10%, the technology should be commercially viable.
Researchers at University of Illinois-Chicago and Northwestern University have engineered an artificial ribosome, Ribo-T, with the two subunits tethered to each other. It works as good as a real ribosome and it could be tuned to produce unique polymers, to study ribosome function or to produce novel therapeutics. In two surprising observations, it was noted that Ribo-T could support assembly of a functional ribosome in the cell and that it could even support growth in the absence of the actual ribosomes. This is a revolutionary approach to expand the genetic code and offers exciting opportunities for synthetic biology.
Here’s an interactive review of science in 2015 and features AI, space exploration, drones, CRISPR, and Elon Musk.