open position: Bioinformatics and/or Computational Biology

The Evolutionary Biology Lab at the Instituto Gulbenkian de Ciência (IGC) is recruiting for a position in Bioinformatics and/or Computational Biology.

We are seeking a highly motivated person with experience in analysis of genomics data of prokaryotes to work at the IGC, in the context of a collaborative project between Isabel Gordo (Principal investigator of the Evolutionary Biology Lab) and Michael Lassig (Principal investigator of the Statistical Physics and Quantitative Biology Lab at the University of Cologne).
The ideal candidate should have a PhD in the field of Bioinformatics or Computational Biology, research experience in NGS data analysis or modelling of microbial evolution. Candidates with a Ms degree will also be considered if they have experience in this field.

The successful applicant will be fully integrated in the team working in Gordos Lab, actively participating in lab meetings, seminars and training. S/he will also interact closely with members of Lassig´s Lab and collaborators of the Collaborative Research Centre (SFB) 1310 Predictability in Evolution. To fulfil this role, s/he will be given a high degree of responsibility and freedom.

S/he will be encouraged to undertake periodic visits to the University of Cologne to strengthen the international collaborations that have been established in Gordo´s Lab. Fluency in English (written and spoken) is required.

The fellowship will have the duration of 12 months with possibility of extension at the end of this period, for a maximum of 3 years. The successful candidate will be contracted on the basis of exclusivity as regulated by the directives of the Instituto Gulbenkian de Ciência (www.igc.gulbenkian.pt).

Applications should be sent by email to igordo at igc.gulbenkian.pt with the subject: Bioinformatician IGC-Cologne. The application should consist of one PDF file including a motivation letter, CV and the contact of two previous supervisors (mentors or teachers in the case of a Ms holder). Potential candidates will be pre-selected on the basis of CV and motivation letter, and selected candidates will be called for interview.

Selected best review of 2018 at Trends in Microbiology: Evolutionary Mechanisms Shaping the Maintenance of Antibiotic Resistance

Evolutionary Mechanisms Shaping the Maintenance of Antibiotic Resistance

Recommended by Gail Teitzel, Editor of Trends in Microbiology

Antibiotic resistance is a bedevilling problem due to continued emergence of new resistance mechanisms and the spread of resistance leading to bacterial infections that are more difficult to treat. While these mechanisms are valuable to a bacterium to have in the presence of a particular antibiotic, these mutations are often costly to maintain. Yet they continue to be maintained in the absence of antibiotic stress. This review by Paulo Durão, Roberto Balbontín, and Isabel Gordo in Trends in Microbiology addresses this conundrum of how antibiotic resistance mechanisms are maintained, including compensation mutations and epistatic interactions. I enjoyed this in-depth view of the discussion of costs and compensations for how it could be used to think about better use of existing therapeutic options and developing new agents for the pressing problem of antibiotic resistance.

A link to the blog:

http://crosstalk.cell.com/blog/best-reviews-we-published-in-2018-part-2

 

Recommended by F1000: Our new Review on Evolutionary mechanisms shaping the maintenance of antibiotic resistance

F1000 Recommendations:

“This is an exceptionally well-written review of the evolutionary mechanisms influencing the maintenance of antibiotic resistance, focusing on the fitness cost, compensatory evolution, epistasis, and environmental effects on these evolutionarymechanisms. The review provides an accessible introduction to those in the field of antimicrobial resistance (AMR) who have yet to consider (to any significant degree) the evolutionary mechanisms behind resistance generation and maintenance. However, it is no doubt a valuable review for all in the field, with excellent references and clear figures.
I would recommend this as mandatory reading for all in the field of AMR: students and their supervisors, alike! I feel the review serves as a call to researchers to conduct studies that target the critical knowledge gaps highlighted in the review. It also speaks to the funding bodies calling for an improved understanding of the fundamental science of AMR evolutionary mechanisms, as this can provide insights into novel drug targets as well as more informed risk assessments, which will inevitably lead to more appropriate and cost-effective mitigation strategies.”

- Andrew C Singer

“This is an excellent and thorough review on the evolutionary mechanisms that allow (and determine) antimicrobial resistance. It provides an excellent introduction to the range of factors and mechanisms involved and will be useful to students beginning research projects and experienced researchers alike.”

- Adrian Mulholland

 

Welcome Dragan!

We are happy to welcome Dragan who is starting as a PostDoc  in the project “PREPARE – Predicting the Persistence of Resistance across Environments”, financed by the Fundação para a Ciência e Tecnologia (FCT).

Promoting a free online course on Antibitic Resistance (Institut Pasteur)

Greetings from Paris!

I am Sebastian Aguilar, a postdoc in the genomes and genetics department. I am trying to promote a free online course on «resistance to antibacterial agents » that Insitut Pasteur and Paris Diderot are putting together. The course is in English, lasts 6 weeks and requires only a couple of hours/week effort. The course is open to everyone interested in antibiotic resistance (although a bachelor in science is recommended) and certificates are available. I am the community manager for this course and I will be more than happy to answer any questions you would have.

Please find here the link to the course or paste to the browser:

https://www.fun-mooc.fr/courses/course-v1:pasteur+96009+session01/about

Evolution Rewind!

Recurrent Reverse Evolution Maintains Polymorphism after Strong Bottlenecks in Commensal Gut Bacteria

Abstract

The evolution of new strains within the gut ecosystem is poorly understood. We used a natural but controlled system to follow the emergence of intraspecies diversity of commensal Escherichia coli, during three rounds of adaptation to the mouse gut (∼1,300 generations). We previously showed that, in the first round, a strongly beneficial phenotype (loss-of-function for galactitol consumption; gat-negative) spread to >90% frequency in all colonized mice. Here, we show that this loss-of-function is repeatedly reversed when a gat-negative clone colonizes new mice. The regain of function occurs via compensatory mutation and reversion, the latter leaving no trace of past adaptation. We further show that loss-of-function adaptive mutants reevolve, after colonization with an evolved gat-positive clone. Thus, even under strong bottlenecks a regime of strong-mutation-strong-selection dominates adaptation. Coupling experiments and modeling, we establish that reverse evolution recurrently generates two coexisting phenotypes within the microbiota that can or not consume galactitol (gat-positive and gat-negative, respectively). Although the abundance of the dominant strain, the gat-negative, depends on the microbiota composition, gat-positive abundance is independent of the microbiota composition and can be precisely manipulated by supplementing the diet with galactitol. These results show that a specific diet is able to change the abundance of specific strains. Importantly, we find polymorphism for these phenotypes in indigenous Enterobacteria of mice and man. Our results demonstrate that natural selection can greatly overwhelm genetic drift at structuring the strain diversity of gut commensals and that competition for limiting resources may be a key mechanism for maintaining polymorphism in the gut.

The new article on the order of mutations in E.coli adaption to the gut has been published in PLOS Genetics!

A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut

Abstract:

The relative role of drift versus selection underlying the evolution of bacterial species within the gut microbiota remains poorly understood. The large sizes of bacterial populations in this environment suggest that even adaptive mutations with weak effects, thought to be the most frequently occurring, could substantially contribute to a rapid pace of evolutionary change in the gut. We followed the emergence of intra-species diversity in a commensal Escherichia coli strain that previously acquired an adaptive mutation with strong effect during one week of colonization of the mouse gut. Following this first step, which consisted of inactivating a metabolic operon, one third of the subsequent adaptive mutations were found to have a selective effect as high as the first. Nevertheless, the order of the adaptive steps was strongly affected by a mutational hotspot with an exceptionally high mutation rate of 10-5. The pattern of polymorphism emerging in the populations evolving within different hosts was characterized by periodic selection, which reduced diversity, but also frequency-dependent selection, actively maintaining genetic diversity. Furthermore, the continuous emergence of similar phenotypes due to distinct mutations, known as clonal interference, was pervasive. Evolutionary change within the gut is therefore highly repeatable within and across hosts, with adaptive mutations of selection coefficients as strong as 12% accumulating without strong constraints on genetic background. In vivo competitive assays showed that one of the second steps (focA) exhibited positive epistasis with the first, while another (dcuB) exhibited negative epistasis. The data shows that strong effect adaptive mutations continuously recur in gut commensal bacterial species.

Antibiotic resistance may be a consequence of interaction with the immune system

Our new papers on enhanced survival of resistant bacteria macrophages and the evolution of small colony variants have been covered in the national press:

https://lifestyle.sapo.pt/saude/noticias-saude/artigos/resistencia-de-bacterias-aos-antibioticos-e-ao-sistema-imunitario-esta-interligada

http://www.dnoticias.pt/hemeroteca/597114-resistencia-de-bacterias-aos-antibioticos-e-ao-sistema-imunitario-esta-inter-DGDN597114#

http://sicnoticias.sapo.pt/pais/2016-06-30-Resistencia-de-bacterias-aos-antibioticos-e-ao-sistema-imunitario-esta-interligada

http://www.biotechniques.com/news/Macrophages-Induce-Antibiotic-Resistance/biotechniques-364982.html#.WQNW31PyuRs