Benjamin Kottler

Summary

I grew up in Paris and moved to Brisbane in 2010.

I have always been interested in science in general but I was never sure about which topic I wanted to study. That is why my university program is slightly unusual. I started with a technical degree in biochemistry, which allowed me to learn how to efficiently manage several techniques. During this course I had the unique chance to work with Prof. Patrick Forterre on archaebacteria, trying to unravel the mystery of the origin of life. Retrospectively I have to strongly thank him for showing me how to love research. That’s why I continued my education in science.

I went to the University Paris-7 Denis Diderot to study biochemistry, before switching to genetic studies for my Masters. I worked with Dr Regine Terracol at the Institut Jacques Monod in Paris on the bZIP transcription factor Vrille. She showed me the wonderful world of Drosophila melanogaster.

I then chose to focus on Drosophila behaviour and neuroscience for my PhD without any background on neuroscience. I work with Dr Thomas Preat. My project was to discover new genes involved in a particular kind of long-lasting memory called Long-Term Memory (LTM). This involved mastering a wide range of different techniques. I used a behavioural screen based on a pavlovian procedure that pairs odours with electric-shock to selected P-element lines that showed an LTM defect. After a long selection I finally managed to identify specific LTM mutants. I then identified the mutation sites using PCR-rescue, performed molecular studies to analyse the expression of the affected genes. I made RNAi and overexpression lines to confirm the role of these genes in LTM formation, and checked their efficiency in LTM formation by western blot. This long, risky and challenging project made me realize how amazing Drosophila was as a model organism and how to conduct precise and demanding experiments in science.

Finally, from cultivating archaebacteria in a high-pressure sulphite atmosphere, to counting how many flies remembered which odour was associated to an electric shock, I feel that my journey through the world of science and discovery has been very interesting so far.

Research

Now I am continuing to improve my knowledge in the neuroscience field by focusing on the mechanisms of anaesthesia. It is extremely puzzling to realise that we don’t really know how general anaesthetics work and induce the loss of consciousness required for practicing surgery on a daily base. This project involved designing a new behavioural assay and several molecular constructs. I developed a new behavioural paradigm that looks at arousal state under increasing anaesthetic gas concentration while fly activity was recorded with a webcam.  We are able to track single flies (hold in the classical sleep tube) and extract behavioural endpoints relevant to our question, by taking different measurements such as the velocity or distance travelled. This development allows us to work in an almost routine-like manner.

We found that Sleep and General anaesthesia shared more than only behavioural similarities. Short-sleeper flies show resistant to isoflurane compare to controls while long-sleepers show hypersensitivity. This work has been published in Current Biology and highlighted in Nature Reviews Neuroscience, Count backwards from ten…

Moreover this paradigm has been used by Dr Bart van Alphen to study sleep depth in the fly. This study leads to the publication of an article in Journal of Neuroscience and points out for the first time sleep stages in Drosophila melanogaster.

Those 2 articles have been highlighted together in the University of Queensland news.

Finally these works on General Anaesthesia and Sleep lead us to re-think how general anaesthesia might work. We propose a novel hypothesis that general anaesthesia is a two‐step process targeting sleep circuits at low doses, and synaptic release mechanisms across the entire brain at the higher doses required for surgery.

Now we are optimising our current paradigm by improving our behavioural methodology (DART) and following-up our hypothesis of a two-step process for general anaesthesia.

Benjamin KOTTLER CV 2014

Publications

van Swinderen, B., Kottler, B. (2014) Explaining general anesthesia: A two-step hypothesis linking sleep and the synaptic release machinery. BioEssays

Kottler, B., Bao, H., Zalucki, O., Troupe, M., Imlach, W. Paulk, A., van Alphen, B., Zhang, B., van Swinderen, B. (2013) A sleep/wake circuit controls isoflurane sensitivity in Drosophila. Current Biology 23: 594-8.

van Alphen, B., Yap, M., Kirszenblat, L., Kottler, B., van Swinderen, B. (2013) A dynamic deep sleep stage in Drosophila. Journal of Neuroscience 33: 6917-27

Kottler, B, Lampin-Saint-Amaux A, Comas D, Preat T, Goguel V (2011) Debra, a Protein Mediating Lysosomal Degradation, Is Required for Long-Term Memory in Drosophila. PLoS ONE 6(10): e25902. doi:10.1371/journal.pone.0025902

Szuplewski, S., Kottler, B. & Terracol, R. 2003. The Drosophila bZIP transcription factor Vrille is involved in hair and cell growth. Development 130, 3651–3662.