Programme : séminaires et soutenances - Novembre 2014

Programme : séminaires et soutenances - Novembre 2014

Département de Microbiologie,
Institut Pasteur, 25 rue du Dr Roux - 75015 Paris
 

 

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merc. 5 novembre à 14 h 30 : séminaire Emmanuelle CHARPENTIER (Helmholtz Centre, Germany)
 

vend. 7 novembre à 11 h 30 : séminaire Douglas GOLENBOCK (Univ. Massachusetts, Worcester, USA)
 

vend. 14 novembre à 11 h 30 : séminaire Damien DEVOS (Univ. Sevilla, Spain)

 

 

 

 

Emmanuelle CHARPENTIER
Helmholtz Centre for Infection Research (Braunschweig, Germany)

'CRISPR-Cas9 : a bacterial adaptive immune pathway harnessed for genome engineering'

mercredi 5 novembre 2014 à 14 h 30
Amphithéâtre J. Monod - Bât. J. Monod

contact : Patrick Trieu-Cuot (patrick.trieu-cuot at pasteur.fr)


Abstract
The RNA-programmable CRISPR-Cas9 system has recently emerged as a transforming technology in biological sciences, allowing rapid and efficient targeted genome editing, chromosomal marking and gene regulation. In this system, the endonuclease Cas9 or catalytically inactive Cas9 variants are programmed with single guide RNAs (sgRNAs) to target site-specifically any DNA sequence of interest given the presence of a short sequence (Protospacer Adjacent Motif, PAM) juxtaposed to the complementary region between the sgRNA and target DNA. The system is efficient, versatile and easily programmable.

Originally, CRISPR-Cas is an RNA-mediated adaptive immune system that protects procaryotes from invading mobile genetic elements (phages, plasmids). Short CRISPR RNA (crRNA) molecules containing unique genome-targeting spacers commonly guide Cas protein(s) to the invading cognate nucleic acids to affect their maintenance. CRISPR-Cas9 originates from the type II CRISPR-Cas system that has evolved unique mechanisms for the maturation of crRNAs and targeting of invading DNA, identified in Streptococcus pyogenes. On the basis of the discovery of the DNA targeting mechanism, we proposed that RNA-programmable Cas9 could offer considerable potential for genome editing in cells of the three kingdoms of life for biotechnological and biomedical purposes. As demonstrated by a large number of studies published in the last 18 months, DNA targeting by CRISPR-Cas9 has quickly been adopted by the scientific community to edit and silence genomes in a large variety of cells and organisms. I will discuss the biological roles, mechanisms and evolution of CRISPR-Cas9 in bacteria and the applications of the system as a novel genome engineering technology.

 

 

 

 

Séminaire conjoint organisé par les Départements :

Infection et Epidémiologie - Neuroscience - Microbiologie


Douglas GOLENBOCK

University of Massachusetts Medical School (Worcester, MA - USA)


'The Inflammasome drives both a pro inflammatory and anti inflammatory response in Alzheimer’s disease'


vendredi 7 novembre 2014 à 11 h 30

Auditorim du Centre François Jacob

 
contacts :
Jean-Marc Cavaillon / jean-marc.cavaillon at pasteur.fr

Saaid Safieddine / saaid.safieddine at pasteur.fr

Patrick Trieu-Cuot / patrick.trieu-cuot at pasteur.fr



Abstract

Alzheimer’s Disease (AD) is the most important cause of dementia worldwide, affecting nearly 30 million individuals. Neuroinflammation is an important component of AD progression. While the cause of the disease is only partially understood, beta amyloid peptide (A-beta) appears to have a central role in inducing neural inflammation. We have found that A-beta activates the NLRP3 inflammasome in culture. A-beta induced activation of microglial cells not only results in the production of mature IL-1 beta, but results in the inducible death of neurons. Like other NLRP3 activators, A-beta peptide is internalized and causes phagolysosomal instability and pyroptosis. In order to test the role of the NLRP3 inflammasome in AD, we bred APP/PS1 mice into NLRP3 or caspase-1 KOs. KO mice were completely protected from learning and memory deficits. This protection appeared to result from enhanced phagocytosis of A-beta peptide, increased degradation of the peptide by enzymes such as insulin degrading enzyme and reduced amyloid plaque deposition.  Brain levels of IL-1 beta were reduced about 50%. Indeed, microglial cells in NLRP3 and caspase 1 KOs exhibited most of the features of M2 macrophages. In addition, KO mice were protected from abnormalities in long-term potentiation (LTP). While all of the above studies were performed in mice, we found that human brains from patients with Alzheimer’s Disease had evidence of caspase 1 activation. Hence, it appears that the NLRP3 inflammasome plays an important role in the progression of human AD and that inhibition of the inflammasome, or perhaps caspase 1, might be therapeutic.  

 

 

 


Séminaire conjoint des Départements : 'Biologie Cellulaire et Infection' & 'Microbiologie'


Damien DEVOS

Universidad Pablo de Olavide (Sevilla, Spain)


New model organisms: the PVC bacteria superphylum and the evolution of the nucleus.

vendredi 14 novembre 2014 à 11 h 30

Auditorium - Centre François Jacob



contacts : Arnaud Echard (arnaud.echard at pasteur.fr) & Simonetta Gribaldo (simonetta.gribaldo at pasteur.fr)

Abstract
Recently, new questions have arisen and new techniques have been developed in biology, prompting the need for novel model organisms. I will introduce the PVC (Planctomycetes Verrucomicrobia-Chlamydiae) bacterial superphylum. The PVC superphylum comprises widely distributed environmental bacteria withfascinating research potential in evolutionary cell biology, ecology and biotechnology, and human health. In addition to the human pathogens Chlamydiae, members of the Verrucomicrobia have been linked to immune and cell development as well as gut inflammatory conditions and obesity. In addition, PVC members play important roles in the carbon and nitrogen cycling pathways on earth. In this talk, I will particularly highlight their relevance for evolutionary cell biology, as PVC bacteria appear to deviate from our “classical” definition of bacteria in many aspects. Additionally, they might be illuminating for our understanding of the evolution of our own cell. In addition to lacking some “universal” bacterial properties, such as the cell division protein FtsZ and peptidoglycan, some PVC members have a complex and dynamic endomembrane system. I will highlight our recent description of this particular endomembrane system using a multi disciplinary approach, including high-resolution electron microscopy. Eventually, I will speculate about how this bacterial endomembrane system could be linked to the origin of the eukaryotic nucleus.

. Evolution of the nucleus. Devos DP, Gräf R, Field MC. Curr Opin Cell Biol. 2014 Jun;28:8-15.
 

. Mind the PVCs. Devos DP, Ward NL. Environ Microbiol. 2014 May;16(5):1217-21.


. PVC bacteria: variation of, but not exception to, the Gram-negative cell plan. Devos DP. Trends Microbiol. 2014 Jan;22(1):14-20.


. A bacterial tubulovesicular network. Acehan D, Santarella-Mellwig R, Devos DP. J Cell Sci. 2014 Jan 15;127(Pt 2):277-80.


. Three-dimensional reconstruction of bacteria with a complex endomembrane system. Santarella Mellwig R, Pruggnaller S, Roos N, Mattaj IW, Devos DP. PLoS Biol. 2013;11(5):e1001565.


. Evolution. Intermediate steps. Devos DP, Reynaud EG. Science. 2010 Nov 26;330(6008):1187-8.


. Endocytosis-like protein uptake in the bacterium Gemmata obscuriglobus. Lonhienne TG, Sagulenko E, Webb RI, Lee KC, Franke J, Devos DP, Nouwens A, Carroll BJ, Fuerst JA. Proc Natl Acad Sci USA. 2010 Jul 20;107(29):12883-8. Epub 2010 Jun 21.


. The compartmentalized bacteria of the planctomycetes-verrucomicrobia-chlamydiae superphylum have membrane coat-like proteins. Santarella-Mellwig R, Franke J, Jaedicke A, Gorjanacz M, Bauer U, Budd A, Mattaj IW, Devos DP. PLoS Biol. 2010 Jan 19;8(1):e1000281.

 

 

Mis à jour le 31/10/2014

Agenda

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