New research using a modified Cas9 protein has shown that with the proper tools, geneticists have unprecedented access to edit the epigenome.1 Accessing the epigenome is a treasure trove of research on the same scale as CRISPR. However, utilizing this new research to maximum effect will require a comprehensive software platform to unify the various data elements required for genetic engineering in the epigenome.
The epigenome is recognized as a fruitful area for basic research and disease-targeted research alike. The new research uses a targetable complex of Cas9 and TET1 in order to methylate or demethylate promoter sequences which cause transcriptional changes of the targeted sequence by disrupting DNA coiling. The new research is especially notable for taking place within mouse muscle cells and neurons, meaning that future research won’t have to struggle making it work in eukaryotes or even other model animals. Even more impressively, the new research went farther than a proof of concept, and was proven both in vitro and in vivo.
Cracking the Epigenome
The epigenome is an area of particular interest to geneticists and molecular biologists because of its well-documented status as the mediator between external environmental factors and genetic changes. A number of landmark studies in mice indicate that the epigenome is responsible for “genetic memory”, and can be as granular as a mouse pup “remembering” the scent signature of its father even when kept in isolation. Pretty impressive, yet we know hardly anything about the impacts of epigenomics in humans.
The epigenetic studies in mice have inspired a gold-rush of research, and with good cause. Expect genomic DNA-targeted CRISPR therapeutics to pull through into the clinic first, though: the epigenome is far less understood and far more difficult to manipulate than genomic DNA. With the new research, we’ll be able to start filling in the blanks of the human epigenome.
Because there are multiple mechanisms of epigenetic silencing or activation, there are a number of different approaches to epigenetic editing aside from the technique outlined by the new research. Molecular biologists will probably scoff at the other options once they get started with the new Cas9 system, though. Zinc finger nucleases and TALENs are still useful in some applications, although they’re unlikely to ever reach the ease of use that the Cas9 based system can provide and they’re notoriously expensive and slow.2 3 The new research builds off prior research into the CRISPR-Cas9 editing system. Scientists knew the CRISPR-Cas9 system was potentially useful for epigenomic editing, but the application was unrealized until now.
The new system doesn’t address the informational complexity of editing the epigenome, however. If anything, you’ll be drowned in even more data than before. Conducting any kind of epigenomic research or development is a bit different from a genomic research project, and requires tracking all of the same data as well as epigenetic-specific data.
To edit the epigenome effectively, you’ll need to track the following pieces of information and be able to sensibly manipulate them in concert:
- Nucleotide and codon makeup of target sequence
- Genomic region of target sequence
- Genomic region of activators/silencers of target sequence
- Physiological conditions which cause target sequence activation or silencing
- Cellular conditions which cause target sequence activation or silencing
- Downstream protein production impact of activation or silencing
- Downstream cellular and physiological impact of activation or silencing, if any
- Primer sequences for target sequence
- Current methylation pattern of target sequence
- Post-editing methylation pattern of target sequence
Editing Environmental Impact
Tracking the basic experimental setup, target sequences and downstream impact of epigenetic editing isn’t enough to get the most out of the new research, however. Even within a single lab handling only the genetic data, each epigenomics experiment will produce multiple data streams:
- PCR data of original target sequence
- PCR data of target sequence after editing
- PCR data of activators / silencers before and after editing
- Sanger sequencing of target sequence
- Sanger sequencing of promoters and inhibitors of target sequence
- Sanger sequencing of target sequence and all associated sequences after editing
- Western blot data of all sequences at all stages of editing
- Transcriptome data before and after editing
- Proteome data after editing
Each epigenetic editing experiment will generate enough data to keep several people busy for several days, even with the current standard of genomic data processing technology. If there are any organization mishaps or snags, it may take quite a while to put all of the data together. It’s clear that the era of epigenetic editing will need a single seamless data stream that is integrated at every level of a laboratory’s functioning.
Experiments in epigenetic editing impact multiple biological systems, and will be studied cross sectionally by many research groups working together on the same project. It’s easy to imagine a research hub in which one group researches the organismic level impact of an epigenetic edit while others study the physiological impact and an other studies the cellular impact while yet an other studies the molecular and genetic impact of a single epigenetic edit.
With this many data streams in a single group and many different groups working in concert, research hubs dealing with epigenomic editing will need an extremely powerful data tracking suite which can also plan experiments, organize responsibilities and ease the analysis and presentation of data. Luckily, there is an information technology platform which can rise to meet the demands of the new age of epigenetic editing.
ScienceCloud is the data tracking, analysis, collaboration and experimental planning software of the future. Using ScienceCloud, you’ll be able to ensure that all of your epigenetic editing experiments are divvied up and executed smoothly. Contact us today to find out how you can use ScienceCloud to join the epigenomic editing revolution and create the next generation of gene therapy.
- “Editing DNA Methylation in the Mammalian Genome.” September 2016, http://www.cell.com/cell/fulltext/S0092-8674(16)31153-9 ↩
- “Targeted DNA Demethylation and Endogenous Gene Activation Using Programmable TALE-TET1 Fusions.” December 2013, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858462/ ↩
- “Optical Control of Mammalian Endogenous Transcription and Epigenetic States.” August 2013, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856241/ ↩