It is widely known that Fleming discovered penicillin by accident. Viagra’s famous effect was initially just a side-effect for an under-development drug against heart attacks, and one of the most famous sweeteners, saccharin, was discovered because Fehlberg forgot to wash his hands while looking for derivatives of coal tar. You can hear similar stories in the discoveries of X-Rays and microwaves. Vulcanized rubber. The strikeable match. Science history is full of serendipity-enlightened revelations.
Our project, Rafts4Biotech, is also a good example to show that sometimes in science you don’t find what you are looking for… but you find something better instead. Daniel López, the project coordinator, discovered bacterial lipid rafts “by accident”. Better to say, by two “accidents”. He started studying melanin production in marine bacteria when biofilms [sticky layers of bacteria with unique properties] got on his way changing the direction of his career. Later, while he was studying these bacterial formations, he ended up discovering some special regions in the membranes of bacteria that were thought to be exclusive of eukaryotic cells that can have endless applications to biotechnology. We interview Daniel to know more about the story and the future of this scientific breakthrough.
Tell us about your beginnings. How did your scientific endeavour start?
I used to study melanin production on a marine bacterium called Marinomonas mediterranea. My aim was to find out how and why this bacterium produced melanin – the pigment found in our skin. First, I thought that this pigment could be involved in UV protection but I saw that the albino mutant was as protected from this radiation as its “tanned” counterpart. By the end of my thesis time, we ended up discovering that this pigment was used as an adhesion molecule and biofilm forming compound. Biofilms were so in at that time! So, I started reading and I got very interested in biofilms. I decided to contact Roberto Kolter in Harvard, who was a leader on the field at the time and I asked him for a postdoctoral position at his lab. He agreed as long as I had my own fellowshipfellowship- so started applying for funding everywhere and ended up receiving a regional fellowshipfellowship I was so happy when I got it because it meant that I was in!
This was the first “accident”: from melanin to biofilms. But how did you end up describing lipid rafts in bacteria?
It was a surprise! It was 2008 and I was studying a mutant that had a defect in some membrane lipid and unable to produce biofilms. We couldn’t find the genetic explanation for these phenotypes so we thought it had to be something more structural.
We saw that not only the biofilm formation pathway was altered but also many other cellular processes like signal transduction, small molecule translocation or protein secretion. When studying these processes under the microscope we saw that they all localized to specific areas of the membrane in normal conditions and were dispersed in the mutant suggesting that the affected lipid could be responsible for the clustering of specific lipids, so that was the first time we started considering membrane areas or micro-domains.
And these microdomains are the famous lipid rafts? Can you explain us what these “rafts” are, we are sure they have nothing to do with inflatable boats!
I explained it to some lawyers the other day and they understood me [laughing]. Any cellular membrane is made of lipids, and they aggregate according to their physicochemical properties. Like oil and water don’t mix, specific lipids stay together forming droplets or domains. These lipid clusters embed membrane proteins conditioning their function, and this specialised membrane structure is what we commonly known as lipid raft. The proteins in a membrane are like the motor in a car, they need the right oil to work, and the lipids in the membrane are precisely like this oil, ensuring that the proteins that they cluster work properly.
And what’s their biological function in bacteria?
I like to use the following example: Imagine you were in Madrid and your mission was to find the person of your life. The chances to meet him/her are almost cero! So many people, pretty much impossible to interact! But if you both go to the same party the chances increase. Lipid rafts are like that party, a small and confined space that increases your chances of meeting. Now we invite flotillin [name of a cellular protein] to the party, flotillin is the friend that both of you have in common. She is a matchmaker that will ensure that you guys meet. So, lipid rafts and flotillin provide the ideal conditions for a protein interaction to happen that otherwise would have very low efficiency or would never happen.
What was the moment when you realized that these domains that you saw could actually be rafts?
When we found flotillin! Flotillin is the orchestra conductor of eukaryotic lipid rafts! It is always in the rafts, is responsible for organising their structure and its essential for their function. So, when we saw that the bacterial homologue of this protein was there we were sure these structures had to be rafts!
And in the moment when you saw the enrichment of flotillin in these areas, were you aware of the magnitude of this discovery? Tell us more about this moment.
Oh yes, when I told my boss Roberto Kolter, that we had flotillin in our structures he was so excited! Well, he [Roberto] was very busy and hardly ever around so our chance to show him our result was in our lab meetings. We had an established schedule for presenting our results, the meetings were on Wednesdays. I thought it was my turn to present so I got to the room but when I saw the confused faces of my colleagues I realised that I was wrong. It was a big deal because I was taking over my colleague’s turn, but when they saw the flotillin results they rapidly forgot about our misunderstanding and they were very excited too. I even remember that Lone Gram was in the room, she is a microbiologist Professor at the DTU (Denmark) and also the granddaughter of the famous microbiologist [Christian Gram] that developed the Gram stain! She was doing a sabbatical with us at the time, and she couldn’t believe her eyes! [laughing] It was a great moment!
And what about the biotechnological application of rafts?
Most current biotechnological processes that occur in bacteria have quite low yields because when we introduce new proteins in the microbial chassis [term used to refer to the modified microorganisms] there are interferences and toxic reactions that lower the efficiency. So now that we know how flotillin recognises and interacts with proteins we can target enzymes of interest to synthetic lipid rafts. Scaling up this to an industrial level we can highly increase the productivity of many reactions like detoxification processes or the production of antibiotics or vitamins.
Rafts have been like a lucky charm for you, they gave you the chance to start your own lab, now you got the chance to coordinate this European project, so what’s next? Are you going to get a Nobel Prize for describing lipid rafts?
Of course! [laughing] No, now seriously, I will be more than happy if one day, in the future, I open a Microbiology textbook and see a small section that says: lipid rafts in bacteria, and that they become an established part of this scientific discipline.