Human genome data would be very difficult to mine unless you had something like RNAi according to Nobel Laureate Craig Mello. He spoke me about his insights into RNAi, new research and what we have yet to discover.
This will be the first time that Prof Craig Mello will visit Stockholm during Nobel Week since he brought home the prize to UMass six years ago. Reminiscing about his previous “whirlwind” visit, he said “it was an incredible experience and I’m really looking forward to going back.”
Mello was honoured along with Andrew Fire for their discovery of RNA interference, now known an RNAi. He calls this the “Google of the cell” as it allows the cell to control information in a similar way to how we surf the web. “We can now enter our own search queries and we can use that to rapidly find genes that are relevant to various types of disease or developmental states.”
Fourteen years after their first paper on RNAi, Mello said “the human genome data, would be very difficult to mine for functional insights unless you had something like RNAi.” It is now being used as a tool in labs all over the world to control gene expression and investigated as a potential therapy. “One of the things that has been really interesting about the development of RNAi is how surprising it was at the beginning and in retrospect we can’t even imagine how the eukaryote cell could function without something like this.”
Audio: Here’s a great insight into Craig Mello as a kid and what blew his mind (Length = 1:24). Listen here:
Much of Mello’s latest research has been on the non-coding genome. “One of the things that is very clear is that epigenetics is extremely important, both in normal development and disease.” He cited cancer as an example of where many genes are inactivated by an epigenetic mechanism though it is still uncertain if small RNA pathways are directly linked to this.
Speaking of his work on piwi-interacting RNA (piRNA), which are a type of non-coding RNA, he said that they establish incredibly stable memories of gene expression that are transmitted from one generation to the next in C. elegans. “You have the off state incredible stable for multiple generations to an extent that it really is almost like the gene has a Mendelian mutation. It behaves differently so we know it’s not Mendelian. These genes are so off that we can actually do genetic screens to look for them to come back on and rather than having a reversal of the epigenetic state, we actually find DNA mutations that alter the silencing pathways to turn these things back on.”
Role in Evolution
One of the many questions that still remains unanswered since the discovery of RNAi, is whether RNA has an impact on evolution. Mello compares our DNA to the hardware for your computer and the RNA and proteins to software.
These are under constant attack according to the Nobel Laureate. Invasive nucleic acids like transposons and retroviruses are constantly entering the cell with the aim of becoming immortal by incorporating into the germline. “You can imagine that that sort of give and take of genetic information which is so important to have in evolution is sort of a double edged sword as if you get something new and it’s useful that’s great but if you get something new and it’s a free-loader, then it’s just going to sit there and use up all your energy to make more copies of itself. Then you’re really in big trouble.”
Audio: Why Craig Mello thinks it’s almost inconceivable that these mechanisms would not have a role in evolution (Length = 2:15). Listen here:
Towards the end of the interview, Mello spoke about evolutionary time and how we, as humans, fit into the history of our planet. “Life on this planet has been pretty much chugging along for 3.8 billion years. There is absolutely nothing that will stop life on this planet as long as there is a niche for it. It’s immortal.”
Most people would be delighted to realise that they were immortal and that they share the same lineage that has existed since the beginning of life on Earth. Being a Nobel Laureate does not mean that you are most people and in keeping with this, Mello’s view is somewhat different. “One of the things that is kind of depressing about humans is we’re so short sighted”.
And finally, Mello gave a piece of advice for all of us short-termed thinkers out there. “Humans really do have the potential to solve problems that would make us more durable and more secure. Right now, it’s not clear to me that we’re paying attention to some of lessons from evolutionary history. You over specialise, you tend to become prone to some major setbacks”.
It is not often that you end a post on a piece of advice aimed at humanity, but when it is an interview with a Nobel Laureate I think it is justified!
Maria Delaney tweets @mhdelaney.