Epigenomics and Synthetic Biology: 2015 in Review

Despite how slow it feels doing it, every year science propels at a startling rate. Here are some paradigm shifts that really impacted my perceptions. Some are a selection of my contributions to EpiGenie and Epibeat, while the rest are written by others from places such as The Scientist and MIT Tech Review.

Epigenomics and Synthetic Biology Breakthroughs:

  1. The labs of Alexander Meissner, J. Keith Joung, and John Rinn brought the non-controversial paper: CRISPR used in human embryonic stem cells to show fundamental difference between mice and men.
  2. Michael Skinner shows that Epigenetics drives genetics straight into evolution
  3. Sperm miRNA Drives Intergenerational Stress Response
  4. A ‘new’ epigenetic mark: 6mA Makes the Grade as a Eukaryotic Epigenetic Mark
  5. DNA Methylation Helps Muscles Remember
  6. The Brain’s Circular RNAs
  7. Epigenome Editing with CRISPR-dCas9, TALEs, and Zinc Fingers
  8. Obesity Alters Sperm Epigenome
  9. CRISPR Gets Creative with Histone Acetylation
  10. Antidepressant Exerts Epigenetic Changes
  11. Move over Optogenetics, here comes Magnetogenetics: Discovery of long-sought biological compass claimed
  12. 5fC is Stable in Mammalian Brains
  13. CRISPR Inversion Untangles How CTCF Controls Chromatin Looping
  14. Epigenetic Clock Goes from Analog to iWatch
  15. New Biotech?! Viral Elements Horizontally Transfer Parasite’s Genes into Non-Standard Host Genomes
  16. RNAi pesticide: ‘Deep inside its labs, Monsanto is learning how to modify crops by spraying them with RNA rather than tinkering with their genes
  17. CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function at Protocadherins
  18. CRISPR-Display: For the lncRNA Enthusiast that has Everything
  19. CTCF Tucks Genes Into Their Lamina Associated Beds
  20. Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides
  21. A DNMT1 (protein) and miRNA complex inactivating the catalytic region
  22. For that question you hear a million times: RNA doesn’t correlate with protein? Huh?
  23. Using Synbio to make narcotics: Brewing Bad
  24. Early Maternal Alcohol Consumption Alters Hippocampal DNA Methylation, Gene Expression and Volume in a Mouse Model
  25. Spray Your Way Free of Cystic Fibrosis with a Gene Editing Nasal Spray
  26. Sex On the Brain: DNA Methylation Defines Gender
  27. New Insights into Puzzling Placental DNA Methylation Domains
  28. 5hmC: a Helping Hand in Drug Addiction
  29. Optogenetic CRISPR/Cas9
  30. Evolving a bigger brain with human DNA
  31. Computed Chromatin Conformation Verfied by CRISPR [Awesome Video]
  32. A Reporter System to Trace Dynamic Changes of DNA Methylation at Single-Cell Resolution

Epigenomic Controversy

Sometimes big ideas need pilots. These pilots need more verification before public exposure but aren’t always uninterpretable, however they should be read with caution in regards to over-interpreting. Small sample sizes aren’t always applicable to a diverse general population and could be noisy but these experiments may start some interesting thoughts and still reveal underlying biology. But sometimes press releases aren’t handled properly.

  1. A paper on Intergenerational Holocaust Effects on Stress Signalling lead to this popular press and then this interesting response.
  2. A talk at ASHG about Epigenomics of Homosexuality got made into popular press and was followed by this critique and subsequent rebuttal.

CRISPR Craze & Crisis

There was  a gene editing summit that called together the leaders of the field. Interestingly it represented a wide variety of the thought spectrum. They came to a conclusion I think most can get behind: don’t start engineering babies clinically, but let the basic research into editing embryos (that don’t go to term) go strong.

Also of interest was the tweeting and blogging of Paul Knoepfler via IPSCell that showed off some of the academic communicative power of social media.

Gene drives have caught my attention as well since they can hijack evolution. They have a lot of potential for disease, with Malaria being the trailblazer. However, they also conjure up images of a dystopia where there’s a new bioterrorism tool in town, capable of specific genocide with just a few genome edited agents needed to ‘infiltrate’ the population.

I’ve also been thinking alot about the designer baby CRISPR CRISIS, it seems that enough of prominet researchers in genomics dismiss the notion of it, since single genes rule very few traits, but I’m still quite worried about myostatin. The condition works in humans, is famous in cows, and has been done in pigssheep, and dogs. It’s just a single gene that can easily make your child athlete of the century or a soldier in a superhuman army. And of course, something about this old Spiderman comic strip reflects on the Stan Lee’s judgement of the current designer baby CRISPR CRISIS:

CVbG-8hWsAA4i4f.jpg-large

 

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Genome Editing Human Embryos

It seems that the ethical buzz was coming from a paper by a unknown Chinese group not involved with any of the genome editing pioneers. They took the unviable leftovers from In Vitro Fertilization (IVF) and then genome edited these human ’embyros’.

Interestingly, the success was quite poor. There was:

  • A Low Editing Rate
  • Toxicity
  • Rampant Off-Target effects

This in stark contrast to the use of CRISPR/Cas9 in dozens of animals ranging the entire tree of life. Ultimately, it doesn’t appear to be human limitation, as mammals including monkeys have been done much more successfully, but rather a result of poor experimental design, as these effects can be almost entirely attenuated by good guide RNA design and it seems that they didn’t considers the different chromatin states of embroynic stem cells that would influence off-target effects.

This was probably due to rushing the design in order to claim to be the first to alter human embryos, as opposed to the much more informative, well done, and ethically appeasing altering of Human Embryonic Stem Cells (HESCs) that showed off human CRISPR/Cas9 genome editing can be done properly in germ-line cells, with all its perks, and lead to breakthrough at the basic level in addition to all the clinical potential of genome editing technologies.

This speculation is apparent as there was a large outcry when the Chinese authors tried the ‘high impact’ journals and it seems they settled on a much lesser known open access that has additional concerns with the peer review process, mainly that it took one day, instead of 6 months to a year of the purgatory that is usually is.

Ultimately, it seems this was rushed for fame of unknown researchers and unknown journal, rather than science. But it’s still a Pubmed indexed journal with an impact factor and published by Springer. It is a bit of a shame as the Pandora’s box of CRISPR in human embryos needed to be opened quite slowly and carefully. The parts are all relatively easily accessible and not restricted, which is what has lead to spectacular pace of CRISPR/Cas9 genome editing development. While the field has its leaders developing CRISPR for the clinic the proper way, the technology it is now at the place where it can be picked up by many more who may not just be interested in the somatic line. But here we are now, waiting to see if genome editing technology will change the world, by curing inherited human disease or being used to design sci-fi nightmares. Either way, human inheritance has entered the designer era.

Sources:

  1. The Primary Publication
  2. Nature News
  3. Stem Cell Assays