A comprehensive assessment of demographic, environmental, and host genetic associations with gut

The gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20-69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition.

A TCR-Dependent Tissue Repair Potential of MAIT Cells.

Three studies published in Cell Reports (Hinks et al., Lamichhane et al., and Leng et al.) describe the transcriptome of human and mouse mucosal-associated invariant T (MAIT) cells after cognate and noncognate stimulation. The results confirm the variability of MAIT cell effector functions and provide evidence of a new tissue-repair gene signature expressed upon T cell receptor (TCR) stimulation.

ipcwswitch: An R package for inverse probability of censoring weighting with an application to

In randomized clinical trials (RCT), the analysis is based on the intent-to-treat principle to avoid any selection bias in the constitution of groups. However, estimates of overall survival can be biased when significant crossover occurs because the separation of randomized groups is lost. To handle these switches, the inverse probability of censoring weighting (IPCW) method has been proposed; however, it is still poorly used in RCT, notably because of its complex implementation. In particular, for time-to-event outcomes, it can be difficult to format data, especially when time-dependent covariates have to be managed, with different measurement times between patients. This paper aims to present the R package ipcwswitch with some guidance for the analysis of the treatment effect on survival in a hypothetical setting where all patients would have continued to take the randomization treatment. After a brief recall of the key principles of the IPCW method, each step of the implementation is described using a toy example. The guidelines are illustrated in a case study that aimed at evaluating the benefit of therapy based on tumour molecular profiling for advanced cancers, SHIVA01.

Circulating Tumor Cells in Early Breast Cancer.

Circulating tumor cells (CTCs) are particularly rare in non-metastatic breast cancer, and the clinical validity of CTC detection in that clinical setting was initially not well recognized. A cytological CTC detection device (CellSearch) fulfilling the CLIA requirements for analytical validity was subsequently developed and, in 2008, we reported the first study (REMAGUS02) showing that distant metastasis-free survival was shorter in early breast cancer patients with one or more CTCs. In the past 10 years, other clinical studies and meta-analyses have established CTC detection as a level-of-evidence 1 prognostic biomarker for local relapses, distant relapses, and overall survival. This review summarizes available data on CTC detection and the promises of this proliferation- and subtype-independent metastasis-associated biomarker in early breast cancer patients.

A review of the use of time-varying covariates in the Fine-Gray subdistribution hazard competing

In survival analysis, time-varying covariates are covariates whose value can change during follow-up. Outcomes in medical research are frequently subject to competing risks (events precluding the occurrence of the primary outcome). We review the types of time-varying covariates and highlight the effect of their inclusion in the subdistribution hazard model. External time-dependent covariates are external to the subject, can effect the failure process, but are not otherwise involved in the failure mechanism. Internal time-varying covariates are measured on the subject, can effect the failure process directly, and may also be impacted by the failure mechanism. In the absence of competing risks, a consequence of including internal time-dependent covariates in the Cox model is that one cannot estimate the survival function or the effect of covariates on the survival function. In the presence of competing risks, the inclusion of internal time-varying covariates in a subdistribution hazard model results in the loss of the ability to estimate the cumulative incidence function (CIF) or the effect of covariates on the CIF. Furthermore, the definition of the risk set for the subdistribution hazard function can make defining internal time-varying covariates difficult or impossible. We conducted a review of the use of time-varying covariates in subdistribution hazard models in articles published in the medical literature in 2015 and in the first 5 months of 2019. Seven percent of articles published included a time-varying covariate. Several inappropriately described a time-varying covariate as having an association with the risk of the outcome.

The level of activity of the alternative lengthening of telomeres correlates with patient age in

All cancer cells need to maintain functional telomeres to sustain continuous cell division and proliferation. In human diffuse gliomas, functional telomeres are maintained due either to reactivation of telomerase expression, the main pathway in most cancer types, or to activation of a mechanism called the alternative lengthening of telomeres (ALT). The presence of IDH1/2 mutations (IDH-mutant) together with loss of ATRX expression (ATRX-lost) are frequently associated with ALT in diffuse gliomas. However, detection of ALT, and a fortiori its quantification, are rarely, if ever, measured in neuropathology laboratories. We measured the level of ALT activity using the previously described quantitative « C-circle » assay and analyzed it in a well characterized cohort of 104 IDH-mutant and ATRX-lost adult diffuse gliomas. We report that in IDH-mutant ATRX-lost anaplastic astrocytomas, the intensity of ALT was inversely correlated with age (p < 0.001), the younger the patient, the higher the intensity of ALT. Strikingly, glioblastomas having progressed from anaplastic astrocytomas did not exhibit this correlation. ALT activity level in the tumor did not depend on telomere length in healthy tissue cells from the same patient. In summary, we have uncovered the existence, in anaplastic astrocytomas but not in glioblastomas with the same IDH and ATRX mutations, of a correlation between patient age and the level of activity of ALT, a telomerase-independent pathway of telomere maintenance.

TGF-β-induced fibrotic stress increases G-quadruplex formation in human fibroblasts.

Scar formation after wound healing is a major medical problem. A better understanding of the dynamic nuclear architecture of the genome during wound healing could provide insights into the underlying pathophysiology and enable novel therapeutic strategies. Here, we demonstrate that TGF-β- induced fibrotic stress increases formation of the dynamic secondary DNA structures called G-quadruplexes in skin fibroblasts, which is coincident with increased expression of collagen 1. This G-quadruplex formation is attenuated by a small molecule inhibitor of intracellular Ca influx and an anti-fibrotic compound. In addition, we identify G-quadruplex-forming sequences in the promoter region of COL1A1, which encodes collagen 1, and confirm their ability to form G-quadruplex structures under physiologically relevant conditions. Our findings reveal a link between G-quadruplexes and scar formation that may lead to novel therapeutic interventions.

Andrea Avila Avila

Junior Group Leader Position (November 2019)

We are seeking to recruit a new group leader at a junior level.

Application deadline: Jan 7th, 2020

Junior Group Leader Position

Bandeau Appel Offres

 

 

 

 

Junior Group Leader Position « Genome Integrity, RNA and Cancer » Unit Institut Curie, France

Institut Curie is constituted of a hospital and a world-class multidisciplinary research center
combining research in cell biology, genetics, epigenetics, immunology, soft matter physics, organic
and medicinal chemistry. It includes over 3,000 researchers, physicians, clinicians, technicians
and administrative staff working on three sites: Paris, Orsay and Saint-Cloud. The institute
facilities include advanced imaging, high throughput sequencing, bioinformatics, reverse phase
protein array, proteomics and mass spectrometry, antibody technologies, cytometry, and
animal housing (platforms). In addition, the hospital proximity allows access to large
clinical databases and sample collections.

Institut Curie is supporting the recruitment of a Junior Group Leader in the « Genome Integrity, RNA
and Cancer » Unit, located at the research site of Orsay (south Paris) in an
exceptional scientific environment within the campus of the Paris Saclay University.

LOGO UMR JPIS

 

 

 

 

 

The « Genome Integrity, RNA and Cancer » Unit is broadly interested in genome integrity and gene
expression. This Unit is in a unique position to describe molecular/cellular
mechanisms that underlie genome biology at unprecedented levels thanks to in-house complementary
expertise in DNA replication, recombination and repair, RNA biology, cytoskeleton control
of cell division and cancer biology. Web site of the Unit: UMR3348

The newly recruited group leader will benefit from state-of-the-art research equipment. Appropriate
laboratory space for 7 people and a start-up package will be available.

Please send a personal statement explaining why you are interested in joining the « Genome
Integrity, RNA and Cancer » Unit, a 3-page research plan, a full CV detailing
publication, patents, invited conferences, awards, grants, training, teaching experience and
contact details of at least 3 individuals who can be contacted for recommendation letters. The
candidates should also indicate how they intend to raise funding, and specify that they meet
criteria to obtain national (e.g. ATIP-Avenir) and international funding (e.g. ERC starting
grants).

Pre-selected candidates will be invited to give a seminar and will be interviewed by an ad hoc
committee in March 2020.

Applications to be sent at: call.umr3348@curie.fr – Deadline: January 7th, 2020

Institut Curie is an inclusive, equal opportunities employer and is dedicated to the highest
standards of research integrity.

HR EXCELLENCE IN RESEARCH

 

Sabrina tenreira

Lucie Hustin

Alessandro Donada

bioinformatic analyst position

NGS data analysis (single cell analysis and genetic lineage tracing ) using shell, Python and R scripts
Handling the QC and organization of the datasets of the team Perié
Handling the QC and pipeline for the single cell plateform
The candidate will work part time for the single cell plateform and part time for the Perié team. He/She will work on multi-omics datasets (single cell RNAseq and Chipseq, cellular barcoding and in situ barcoding dataset) starting from raw datasets to perform bioinformatics analyses (alignment, quantification, QC) on the computing cluster of Institut Curie and further analyze datasets using and optimizing R scripts from the Perié group, as well as developing novel algorithms.
The single cell plateform offers indroplet single cell RNAseq and Chipseq services. The Perié team studies the production of red and white blood cells at the single cell level. In particular, the Perié lab has expertized in several lineage tracing methods in which the candidate will be involved.
Master 2 required at minimum
Applicants must have expertise in high-throughput sequencing computational analyses with capacity to develop scripts in shell, R & Python.Please send a CV, cover letter outlining your motivation and contact for two recommendation to leila.perie@curie.fr before Nov 25th

Vessel co-option in glioblastoma: emerging insights and opportunities.

Vessel co-option is the movement of cancer cells towards and along the pre-existing vasculature and is an alternative to angiogenesis to gain access to nutrients. Vessel co-option has been shown as a strategy employed by some glioblastoma (GBM) cells to invade further into the brain, leading to one of the greatest challenges in treating GBM. In GBM, vessel co-option may be an intrinsic feature or an acquired mechanism of resistance to anti-angiogenic treatment. Here, we describe the histological features and the dynamics visualized through intravital microscopy of vessel co-option in GBM, as well as the molecular players discovered until now. We also highlight key unanswered questions, as answering these is critical to improve understanding of GBM progression and for developing more effective approaches for GBM treatment.

Junior Group Leader Position (November 2019)

We are seeking to recruit a new group leader at a junior level.

Application deadline: Jan 7th, 2020

Junior Group Leader Position

Bandeau Appel Offres

 

 

 

 

Junior Group Leader Position « Genome Integrity, RNA and Cancer » Unit Institut Curie, France

Institut Curie is constituted of a hospital and a world-class multidisciplinary research center
combining research in cell biology, genetics, epigenetics, immunology, soft matter physics, organic
and medicinal chemistry. It includes over 3,000 researchers, physicians, clinicians, technicians
and administrative staff working on three sites: Paris, Orsay and Saint-Cloud. The institute
facilities include advanced imaging, high throughput sequencing, bioinformatics, reverse phase
protein array, proteomics and mass spectrometry, antibody technologies, cytometry, and
animal housing (platforms). In addition, the hospital proximity allows access to large
clinical databases and sample collections.

Institut Curie is supporting the recruitment of a Junior Group Leader in the « Genome Integrity, RNA
and Cancer » Unit, located at the research site of Orsay (south Paris) in an
exceptional scientific environment within the campus of the Paris Saclay University.

LOGO UMR JPIS

 

 

 

 

 

The « Genome Integrity, RNA and Cancer » Unit is broadly interested in genome integrity and gene
expression. This Unit is in a unique position to describe molecular/cellular
mechanisms that underlie genome biology at unprecedented levels thanks to in-house complementary
expertise in DNA replication, recombination and repair, RNA biology, cytoskeleton control
of cell division and cancer biology. Web site of the Unit: UMR3348

The newly recruited group leader will benefit from state-of-the-art research equipment. Appropriate
laboratory space for 7 people and a start-up package will be available.

Please send a personal statement explaining why you are interested in joining the « Genome
Integrity, RNA and Cancer » Unit, a 3-page research plan, a full CV detailing
publication, patents, invited conferences, awards, grants, training, teaching experience and
contact details of at least 3 individuals who can be contacted for recommendation letters. The
candidates should also indicate how they intend to raise funding, and specify that they meet
criteria to obtain national (e.g. ATIP-Avenir) and international funding (e.g. ERC starting
grants).

Pre-selected candidates will be invited to give a seminar and will be interviewed by an ad hoc
committee in March 2020.

Applications to be sent at: call.umr3348@curie.fr – Deadline: January 7th, 2020

Institut Curie is an inclusive, equal opportunities employer and is dedicated to the highest
standards of research integrity.

HR EXCELLENCE IN RESEARCH

 

Ramon Ortiz

Tim Schneider

Selective EGF-Receptor Inhibition in CD4 T Cells Induces Anergy and Limits Atherosclerosis.

Several epidermal growth factor receptor (EGFR) inhibitors have been successfully developed for the treatment of cancer, limiting tumor growth and metastasis. EGFR is also expressed by leukocytes, but little is known about its role in the modulation of the immune response.