January 23, 2014  |  User Stories  |  By  |  0 Comments

Cytobank User Stories: Hervé Luche, Ph.D.

Welcome to Cytobank User Stories, a series featuring interviews with Cytobank users on their research, scientific vision, and use of fluorescence and mass cytometry.

This time we interview Hervé Luche, Ph.D., R&D Manager at the Centre d’Immunophénomique in Marseilles, France.

Send us feedback and let us know who you’d like to hear from (including yourself)!

What are you excited about in science? What is your scientific vision?
Herve Luche,
Herve Luche, Ph.D.

I am very much interested in trying to understand how cells integrate signals and communicate with their environment to actually change their transcriptional programs, fate or acquire a new function. To try to tackle down this complexity in biology, one necessarily needs multi-disciplinary approaches and to combine multiple-expertise. I like sharing ideas with other people of different scientific backgrounds to establish new models and theories. The most exciting part of the work to me is when you bring all pieces of the puzzle together and that your model becomes partly true and clarifies one scientific question. It does not happen very often (to me at least!) but when it does, it is great fun!

What do you study / what is your field?
I studied developmental immunology in the lab of Hans-Joerg FEHLING during my PhD and in the lab of Bernard and Marie MALISSEN for my post-doctoral studies. I engineered two knock-in (KI) mouse strains to address lineage commitment issues, among which a Cre activable RFP line. I combined detection of fluorescent proteins with multi-parametric flow cytometry panels to trace the lineage of reporter positive cells. I applied high resolution flow cytometry schemes with mouse mutants of the TCR signaling pathway and transcriptomic to understand the pattern of genes that were involved in lineage decisions at the molecular level. Recently, I joined the Immuno-phenotyping module at CIPHE, the Centre for ImmunoPHEnomics – (INSERM/US012, AMU, CNRS/UMS3367) in Marseille-Luminy. With its cutting-edge expertise in mouse genetics and immunology, CIPHE aims to develop and analyze, in a massively parallel and standardized mode, mouse KO/KI models allowing understanding the function of the mouse immune system under normal and infectious conditions. CIPHE is a fantastic place to attempt deciphering the immune-phenome of a given gene in the context of an inflammatory response or pathogen challenge. In charge of the R&D of our phenotyping service, I am developing new high content (>15 parameters) flow cytometry panels of immune cells, inflammation models (EAE, DHSS colitis, PEC inflammation). I contribute to national and international phenotyping efforts such as the International Mouse Phenotyping Consortium (IMPC). Finally, I am involved in the development of mass cytometry at CIPHE.
What are some of your favorite papers?
I like papers from HR Rodewald’s lab(1, 2) because they are solid, use multiple genetic tools, and challenge current views in Biology. I like papers of the Malissen lab for the elegant KI approaches that have been used to address biological questions such as the molecular mechanism involved in a T-cell lymphoproliferative disorder (3). I like this review by Maecker et al. because it is very comprehensive and shares advice to reduce experimental variations in multi-parametric flow cytometry studies (4). I also would like to take this opportunity to mention the tremendous work that is currently being done by a world consortium to phenotype in a standardized manner KO mice for every single genes of the mouse genome, as this resource will be instrumental to many scientists reading this post (5) . Finally, this paper by Bodenmiller et al. (6) because it is technically really challenging and demonstrates the full power of mass cytometry technology for a comprehensive signal transduction pathway analysis at the single cell level.
What do you do for fun?
Outdoors, I am fan of bike trips with my wife and kids. A bit tough in Marseille area so we prefer biking along main rivers in Germany in the summer as it is cooler. Mileage is not important there, going at a slow pace to discover landscapes and live this small adventure in family is the key. I also love sea kayaking and hiking in the Calanques.Indoors, I am passionate about history (mainly antic time), especially ages around the discovery of writing in Mesopotamia, but also the rise and falls of antic empires. I like the new trend in history trying to explain big cultural crises such as at the Bronze Age by integrating drastic global changes in weather conditions (Thera volcano eruption), economic crisis brought by cold or draught and resulting poor harvests, the really quick impact of these changes on the human societies ultimately yielding to a cultural downfall. Similar phenomena are now brought up to explain the fall of mezzo-american civilization (Maya) but also the French Revolution due to several consecutive hard winters and bad crop years! Just to make two cents of philosophy and keep in mind that nothing is for given, even in our super high tech civilizations!
What’s your favorite thing about Cytobank?
Having a data sharing platform that is very easy to use is one of the elemental things. Being able to access data from anywhere without having to bring my computer along is another very sweet one. But may be the most successful point is to have one main data analysis platform that is bringing easy ways for biologists to synthesize huge datasets and organize results on a figure using several dimensions. Helping us to make some sense out of this hip of data by supervised and unsupervised analysis, providing visualizations tools that are speaking to many people not doing flow or mass cytometry and all this without any R-scripting skills! I cannot wait for the next visualization tools which will be implemented in Cytobank.

References:

1. Feyerabend TB, Terszowski G, Tietz A, Blum C, Luche H, Gossler A, et al. Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms. Immunity. 2009;30(1):67-79. Epub 2008/12/27. doi: 10.1016/j.immuni.2008.10.016. PubMed PMID: 19110448.

2. Feyerabend TB, Weiser A, Tietz A, Stassen M, Harris N, Kopf M, et al. Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity. Immunity. 2011;35(5):832-44. doi: 10.1016/j.immuni.2011.09.015. PubMed PMID: 22101159.

3. Mingueneau M, Roncagalli R, Gregoire C, Kissenpfennig A, Miazek A, Archambaud C, et al. Loss of the LAT adaptor converts antigen-responsive T cells into pathogenic effectors that function independently of the T cell receptor. Immunity. 2009;31(2):197-208. doi: 10.1016/j.immuni.2009.05.013. PubMed PMID: 19682930.

4. Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the Human Immunology Project. Nature reviews Immunology. 2012;12(3):191-200. doi: 10.1038/nri3158. PubMed PMID: 22343568; PubMed Central PMCID: PMC3409649.

5. Brown SD, Moore MW. The International Mouse Phenotyping Consortium: past and future perspectives on mouse phenotyping. Mammalian genome : official journal of the International Mammalian Genome Society. 2012;23(9-10):632-40. doi: 10.1007/s00335-012-9427-x. PubMed PMID: 22940749; PubMed Central PMCID: PMC3774932.

6. Bodenmiller B, Zunder ER, Finck R, Chen TJ, Savig ES, Bruggner RV, et al. Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators. Nature biotechnology. 2012;30(9):858-67. doi: 10.1038/nbt.2317. PubMed PMID: 22902532; PubMed Central PMCID: PMC3627543.


Interview conducted and presented by Cytobank staff member Angela Landrigan.