That's a very different thing. Let’s start with the basics - what is a CRISPR library? In general terms, it’s a set of genes that have been purposely modified to be able to study a certain condition, such as cystic fibrosis or any other genetically driven disease. These are useful when studying the responses of cells to different drugs, for example. Most of these CRISPR libraries target coding regions present in a genome. That is the DNA or RNA that encode proteins, which are important building blocks for cells as well as the functional work-horses of the body. Proteins will essentially determine how different cell types work and what they look like.
So, we have a good number of these coding region CRISPR libraries. What we don’t have many of are libraries based in non-coding regions. Not only are they difficult to generate chemically, but are expensive and labour-intensive to develop.
Why are they important? We are starting to understand the role of non-coding genes in our genome. These are the genes that do not seem to have a direct function in what our cells look like. However, they do have other functions, which we are now starting to decipher, such as controlling the activity of protein-coding genes. They help determine which genes are turned on or off, and when. Other non-coding regions may be important for protein assembly, which is how the building blocks in our body are created.
Hence, my proposal was: Could we actually develop a library that targets both coding and the important non-coding region at the same time? And, can they be tailored to different people and to different cell types?
Why? Because for different people with different cell types, there will be variations in the DNA or RNA. The question posed here is, can we have a personalised or cell-specific library targeting both the coding and non-coding parts of the genome? That’s the problem that we’re interested in solving at the moment.
This all started in a conversation with another researcher, now an ex-colleague, Junjing Wu, who studies the function of Single Nucleotide Polymorphisms (SNPs) in genes - the substitutions of single letters in our genetic code. Now you see, SNPs are, essentially, the most common type of genetic variation in humans and they tend to be found in the non-coding regions of the genome. Most of the variations don’t seem to have any apparent effect. However, occasionally, these small variations have important implications in the study of human health. For example, a particular SNP can increase susceptibility to environmental factors that cause cancer, or increase the risk of developing diseases such as diabetes. Junjing found so many different streams in her research, she was looking for a way in which we could somehow screen for the SNPs’ function as well when using CRISPR libraries.