Magna Carta then and now
Address to the Friends of the British Library
9 March 2015
One hour talk plus Q&A. Main takeaway points include:
➜ Going from painstakingly aiming for 1x coverage of human genome sequencing to routinely doing 50x coverage of human genome sequencing and 1000x bacterial genome sequencing . . . just for kicks.
➜ Going from painstakingly aiming for 10^-1 to 10^-2 error rates in genome sequencing to routine 10^-9 error rates.
➜ Breaking genome sequencing monopolies with shifts in technology and aiming for MinION nanopore + protein motor sequencing architectures for the next disruption measuring pico-Amperes per base pair.
➜ Going from 30x coverage of a human genome sequence taking up 9 Terabytes of data, down to 2.5 Megabytes of data per human genome sequence . . . as compared to the human reference genome. That's right, the relative information content of your genome is 2.5MB. Our whole species population is 2 Petabytes.
➜ Using CRIPSR in conjunction with human organoids on microfluidic chips and vastly exceeding the sophistication of conventional tissue culture models by including mechanical stressors for example.
➜ Using CRISPR to quickly identify the single base pairs that are responsible for particular genetic disorders, and restoring the disease phenotype to healthy by adding correctly coded mRNAs.
➜ Sequencing entire genomes to identify off-target modifications caused by unintentional CRISPR edits, and trying to avoid any modification of tumour suppressor genes or activating oncogenes.
➜ State of the art for CRISPR off-target modification is zero in 3x10^14 base pairs, possibly higher, and this only with off-the-shelf CRISPR: paired nickases etc are better CRISPRs that result in much better specificity, many orders of magnitude more specific.
➜ Aging as the universal disease. Co-opting common alleles from supercentenarians. Co-opting parabiosis findings such as GDF11 that reverses many age-related problems. Influencing mitochondrial homeostasis with small molecules such as nicotinamide or using CRISPR to induce equivalently useful epigenetic changes. Dialing changes and gene expression up and down to 47 fold greater or less.
➜ Out-of-date CRISPR technology is anything greater than 3 months old: innovating at a tremendous rate.
➜ Multiple transcriptional activation domains bound to dead CRISPR (CRISPR that binds DNA but doesn't cleave DNA) can result in 20,000-fold upregulation of gene activity, e.g. for the human titan gene that is 100,000 base pairs long and almost impossible to deliver via gene therapy.
➜ Examining asymmetric distribution of individual proteins and RNAs via subcellular localisation of these biomolecules using confocal multi-layer imaging and expansion microscopy and getting down to 10nm imaging resolution of 3D cells.
#crispr #syntheticbiology #genomics
- Emory UniversityPost Doc, Chemistry Dept., 2011 - 2013
- University of PretoriaPost Doc, Biochemistry Dept. Malaria Research Group, 2010 - 2011
- Meraka Institute, CSIRScientific Officer, HPC Research Group, 2008 - 2010
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