Coming from the Rockefeller University in NY, Matthieu Louis leads the Sensory Systems and Behaviour group at the CRG, the only lab in Barcelona, and one of the few in Spain, investigating Drosophila neuroscience. His team comprises eight people with backgrounds in molecular biology, engineering and physics. Their aim is to correlate neural circuit function with behaviour using fruit fly larvae. “The Drosophila larva has a repertoire of complex behaviours and key cognitive functions. Yet its nervous system has 10 million neurones fewer than humans”, explains the physicist.
The group tries to understand how odours are encoded by the olfactory system. Features such as quality, “Does this smell like banana?”, and intensity, “Is this a morsel of banana or a bunch?”, are efficiently represented by only 21 olfactory sensory neurones, so that the larva can distinguish between hundreds of food-related odours. The researcher says that there must be a combinatorial code, yet it does not seem to be as trivial as the activation of different combinations of neurones by distinct odours. “We have evidence that the nature and the intensity of an odour is represented not only by the identity of the sensory neurones it activates, but also the way each one is activated”, he explains.
From information processing to chemotaxis
Once a smell has been encoded, it has to be processed. To find the higher-order neurones involved in the integration of olfactory information, the group is undertaking a large behavioural screen. They test thousands of fly lines in which subsets of neurones are inhibited or over-activated. They then characterise how these perturbations affect chemotaxis, the orientation behaviour observed in response to an odour gradient. To decide whether to go straight ahead or turn, the larva monitors information about odour concentration changes. When a wild-type animal detects an intensity increase of an attractive odour, it keeps going forwards, but, as the group has recently described, if the odour intensity decreases the larva reorients through an active-sampling mechanism: much like rats and dogs, the larva sweeps its head laterally to check intensity levels on either side.
With their screen, the researchers are looking for mutants showing reorientation defects. To that end, they have developed their own computer-vision software. “We needed an algorithm to quantify subtle movements of the head and body posture with a high space-time accuracy. As no tool like this existed, we spent a year developing one”, says the head of the group.
“If we understand the neural logic of larval chemotaxis well enough, we should be able to synthetically produce predictable behavioural sequences”. Such a model could be useful for robotics. “Currently, dogs are trained to find mines. We could design robots that navigate spatially, searching for the chemical compounds present in explosives”.
Many questions remain to be answered before this becomes reality. How does the larva integrate a series of stimuli (touch, light, heat, smell) that are received simultaneously before deciding what to do next? And how is sensory input converted into motor output? “There are many challenges ahead. But it is thrilling to witness the genesis of a decision in a minibrain, from elementary spikes in sensory neurones down to the coordinated contraction of dozen of muscles. Flies have much to teach us about the function of our own brain”, concludes the Belgian researcher.
This article was published in the El·lipse publication of the PRBB.
An interview recently published in Ellipse, the monthly magazine of the PRBB.
Born in Argentina 59 years ago to a Galician father and a mother from Madrid, Fernando Giráldez grew up between Buenos Aires, Santander, Madrid and Valladolid, where he studied medicine. Ten years ago he joined the CEXS-UPF, where he became director from 2003 until 2006. His hobbies are cooking, history and marathon-running.
Did you always want to be a scientist?
I chose medicine because it straddles the sciences and humanities. In the seventies, research was still a dream, only done by a few professors in universities. One of them, Carlos Belmonte, from the University of Valladolid, got me hooked.
Was it hard to choose between the lab and the clinic?
During my military service I was in a neurosurgery unit and I practised clinical medicine. I admire doctors a lot, but I like basic research and the academic life more. Looking back, maybe I would have liked to do research that was closer to medicine.
What was your first research about?
I did my thesis on the electrophysiological properties of corneal pain receptors. At Cambridge, I continued to study cell membranes and I got even more into the tradition of biophysics.
From Cambridge you came back to Valladolid.
In 1983 I joined the world of development. Firstly, doing electrophysiology on the otic vesicle (the precursor of the ear). From there I moved into studying growth and cell proliferation and, later on, the molecular biology of development. Quite a change!
You saw the great transformation of biology…
In the nineties great changes in molecular biology reached vertebrate embryology: the capacity to see and manipulate genes. We changed from only being able to see things, to beginning to understand the mechanisms. It was really interesting to live through this not only technical but also intellectual transformation.
What has your greatest contribution to the field been?
We incorporated in vitro techniques and this led to the identification of growth factors essential for the development of hearing. After this, we contributed to the knowledge of the first stages of sensory cell and auditory neurone development.
As well as doing research, you also teach.
I love teaching. In the second year of my degree I started giving classes to other students and I haven’t stopped since. Explaining something that took me a lot of effort to understand and seeing that in a couple of days the students are able to talk about it confidently is very gratifying.
What does being located in the PRBB offer?
There is magnificent infrastructure here and lots of informal help between the scientists, exchanges of ideas and techniques. In a less tangible way, the PRBB collectively imposes high standards. The better the people around you are, the better you are yourself.
What do you need to do research?
A modicum of ability, a certain level of ambition and the will to excel, a good dose of work and perseverance. But you learn research by doing it and there’s nothing better than doing it alongside good people, who set the standard.