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Marie Curie Early Stage Researcher position in Palaeoproteomics

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This project has received funding from the European Union's EU Framework Programme for Research and Innovation Horizon 2020 under Grant Agreement No. 861389 - PUSHH

 

One PhD position is available at the University of Bordeaux starting September 1st, 2020 as a part of the European Training Network PUSHH Palaeoproteomics to Unleash Studies on Human History funded by the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement No 861389. This vacancy offers a three year, fully funded PhD on Mass Spectrometry for Palaeoproteomics (reference ESR10). You will be supervised by Prof Caroline Tokarski with cosupervision by Prof Jane Thomas-Oates.

 

About PUSHH:

The PUSHH ETN builds on the recent exciting advances in “palaeoproteomics”, i.e. mass spectrometry based ancient protein sequencing. PUSHH will develop new proteomic methods, optimised for ancient protein analysis, that will be applied to address outstanding evolutionary questions in human and hominoid evolution. Currently, there are very few specialists that have been trained to analyse ancient proteins, but the growing demand for information provided by palaeoproteomics will require highly qualified profiles with backgrounds in analytical chemistry, bioinformatics, palaeoanthropology and palaeontology. PUSHH will fill this advanced training gap by providing international, and intersectoral doctoral (PhD) training, for 14 Early Stage Researchers (ESRs) in seven different EU countries. PUSHH will guide the ESRs to develop the advanced interdisciplinary competence they need to achieve seamless integration of palaeoproteomics with the established research approaches currently used in palaeoanthropology and archaeology.

Read more about the network at: www.pushh-etn.eu

 

Project description:

The latest generation of high-resolution tandem mass spectrometry for palaeoproteomics can reliably and rapidly detect proteins in complex mixtures, even in the very limited quantities typical of ancient samples. Workflow miniaturization and simplification of sample preparation, by integrating into a single or few step(s) different chemical treatments, have already been proven to improve recovery in the most recalcitrant ancient samples. Such approaches are contributing to minimizing the amount of starting material needed for palaeoproteomics analysis. The possibility to combine the dissociative capabilities of complementary fragmentation methods (ETD, UVPD, HCD) maximises the ability to elucidate the full complexity of the protein material, in sequence, in polymorphism and in chemical and/or post-translational modifications with unprecedented depth and accuracy. Top-down methods, adding molecular details lost when proteoforms are hydrolyzed into proteolytic peptides in bottom-up proteomics, also benefit from the recent technological gains in mass spectrometry. The ESR10 will develop new minimally invasive methods and miniaturized analytical workflow based on bottom-up and top-down approaches, to analyse trace level of proteins in palaeoanthropological and palaeontological materials and reach an exhaustive characterization of ancient material available. Digestion free top-down proteomics methods will also be investigated to remove many of the limitations hampering analysis of this category of samples. The methods will be used to identify proteins from samples with very limited amounts. Elucidation of protein polymorphism will also be studied with these minimally invasive methods in partnership with the PUSHH partners. Another application of these methods is the study protein degradation (e.g. chemical modifications, breakdown) such as the degradation of tooth enamel proteins in partnership with ESR14.

 

Environment and place of employment:

Place of employment: The Institute of Chemistry and Biology of Membrane and NanoObjects (CBMN), UMR CNR 5248 and Proteome Platform of the University of Bordeaux.

Expertise of the laboratory team and platform: “Omics” developments based on high-end technologies applied to various fields (biology, chemistry, medicine, pharmaceutical science, plant science, environment, cultural heritage) from sample preparation to (bio)macromolecular identification, targeted/non-targeted quantitative analysis and intact protein characterization using top-down analysis. Website: https://proteome.cgfb.u-bordeaux.fr/en/proteome

 

Job description:

- Carry out an independent research project under supervision.
- Complete PhD courses or other equivalent education corresponding to approx. 30 ECTS points.
- To document work appropriately and in accordance with research best practice.
- To prioritize tasks within an agreed work schedule to ensure that the project(s) are delivered on time. Submit the thesis by the deadline.
- Deliver scientific articles and/or book chapters in collaboration with other PUSHH ESRs and supervisors.
- Communicate your scientific activity to a broad audience (e.g. outreach activities).
- Actively attend all the mandatory network-wide PUSHH activities, which will take place in multiple locations in and outside Europe.
- Travel for a mandatory secondment period at another institution within the PUSHH consortium. Actively take part in the research projects involving multiple institutions and ESRs within the PUSHH network.

 

Additional information

Eligibility criteria:

To be eligible for a PhD position in PUSHH on 1st September 2020, you must:

- be in the first four years (full-time equivalent research experience) of your research career, and have not been awarded a doctoral degree.
- have not resided or carried out your main activity (work, studies, etc.) in France for more than 12 months in the preceding three years. Compulsory national service or short stays such as holidays are not taken into account.

 

Selection process

The following documents have to be sent by e-mail to Prof Caroline Tokarski (PhD supervisor) at the following address: caroline.tokarski@u-bordeaux.fr:

- Detailed CV including education, experience and skills relevant for the position.
- Cover letter (maximum 2 pages).
- Diploma and transcript of records.
- Names of two Professional References and their contact information.

After the expiry of the deadline for applications, the authorized recruitment manager selects applicants for assessment on the advice of the hiring committee. All applicants are then immediately notified whether their application has been passed for assessment by an unbiased assessor. Interviews are expected to be held. The assessor makes a non-prioritized assessment of the academic qualifications and experience with respect to the above-mentioned area of research, techniques, skills and other requirements listed in the advertisement.

 

Web site for additional job details

http://www.pushh-etn.eu

 

Requirements

Offer Requirements:

REQUIRED LANGUAGES

ENGLISH: Good

Skills/Qualifications:

Qualifications:

- Chemistry or biochemistry Master Degree or equivalent

Knowledge:

- Demonstrated knowledge of analytical chemistry, including mass spectrometry and liquid chromatography techniques (theoretical and experimental)
- Knowledge of, and demonstrated experience in designing, implementing, and optimizing: (i) analytical methods for protein characterization, (ii) biochemical methodologies for sample preparation for protein analysis.
- Knowledge of tandem MS-based proteomics data generation, interpretation and statistical validation.
- Experience in detection and identification of protein residues from cultural heritage by proteomics is a valued plus.

Skills:

- Ability to comfortably work in a highly interdisciplinary environment.
- Good communication skills in written and oral English is required.
- Integrity, motivation, organization, and good collaboration skills.
- Ability to develop contacts to enhance knowledge and understanding and form relationships for future collaboration.

 

More information and to apply for this job: https://euraxess.ec.europa.eu/jobs/527729

PhD fellowship in High Resolution Mass Spectrometry applied to Cultural Heritage (M/F)

General information

Reference : UMR5248-CARTOK-005
Workplace : BORDEAUX
Date of publication : Tuesday, June 02, 2020
Scientific Responsible name : Caroline Tokarski
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 September 2020
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

 

Description of the thesis topic

The analysis of Cultural Heritage samples is crucial for the understanding of artists' technique, the conservation and the preservation of artworks. The studied artworks are priceless and the sample size available for analysis is extremely low, thus requiring the development of the most efficient, informative and robust analytical methodologies.
The PhD project proposes to decipher the complexity of Cultural Heritage organic materials using unexplored developments in both chemistry and high resolution mass spectrometry to achieve structural information on the biological compounds in their environments and to map their degradation state. One of the challenges is linked to the chemical decoding of the organic molecular network. Applied to the study of artworks, this information will have a major impact on the understanding of artworks' construction, composition and degradation, and will aid in determining preservation conditions (conservation treatment and storage).
This proposed research will exploit the latest technical developments in high-resolution mass spectrometry as well as alternative fragmentation modes (ETD, UVPD) for the study of intact or transformed biomolecules found in cultural heritage material.
The major objectives of this PhD project are the development and optimization of: (i) fully-adapted and original sample preparations tailored to the study of very small sample amounts (trace analysis), to circumvent the complex inorganic/organic nature of the formulated materials of interest and (ii) top down methods to study proteins modifications, breakdowns, cross-linkings and their relationship to the surrounding matrix made of mixtures of organic and inorganic compounds. To help in this complex task, development of customized software solutions will be proposed in collaboration with bioinformatics experts (local and European collaborations).
This PhD project will address specific questions about material manufacture or origin (i.e. to gain knowledge on the formulations of the master artists or societal information) and its degradation state (i.e. effect of particular conservation treatments).
The candidate will have to interact with art conservators, historians and archaeologists from the partners' museums within an interdisciplinary research environment.
The project will require careful development of activities for public engagement as well as writing scientific articles, papers, reports or books, as appropriate.

 

Work Context

Place of employment: The Institute of Chemistry and Biology of Membrane and NanoObjects (CBMN), UMR CNR 5248 and Proteome Platform of the University of Bordeaux.

Environment: The project will benefit from the exceptional environment of the CNRS International Associated Laboratory ARCHE with The Metropolitan Museum of Art, New York, U.S.A. (Co-Directors: J. Arslanoglu, C. Tokarski, open in 2019).

Expertise of the laboratory team and platform: “Omics” developments based on high-end technologies applied to various fields (biology, chemistry, medicine, pharmaceutical science, plant science, environment, cultural heritage) from sample preparation to (bio)macromolecular identification, structural analysis, targeted/non-targeted quantitative analysis and intact protein characterization using top-down analysis. Website: https://proteome.cgfb.u-bordeaux.fr/en/proteome.
Considering Cultural Heritage: coordinator /partner of cross-disciplinary projects and European networks (JPI-JHEP LeadART, ETN TEMPERA, ETN PUSHH, IPERION HS), organization of the 1st School and associated Symposium on Advanced Mass Spectrometry Applied to Cultural Heritage involving a consortium of pioneer researchers in the field (https://hrms-heritage2019.org/; http://bss-appliedchemistry.u-bordeaux.fr/en/Bordeaux-Summer-Schools/r969.html).

 

Constraints and risks

None

 

Additional Information

Essential and Preferred Experience and Skills:
- Chemistry or biochemistry background
- Demonstrated knowledge of analytical chemistry, in particular, mass spectrometry and chromatography techniques (theoretical and experimental).
- Demonstrated experience in tandem MS-based proteomics data generation and analysis is a valued plus.
- Demonstrated experience in interpretation of MS/MS data, bioinformatics analysis and statistical validation of the results is a valued plus.
- Strong or demonstrated interest in art and art preservation is a valued plus.

Other Skills:
- Good communication skills in written and oral English is required.
- Integrity, motivation, organization, and good collaboration skills.
- Ability to comfortably work in a highly interdisciplinary environment with colleagues with different scientific and non-scientific backgrounds.
- Knowledge of use and conservation of proteinaceous materials in art and archaeology is a valued plus.

Elegibility:
Selection process steps:
- Pre-selection based on the applicant's CV and cover letter
- Interview (video conference or personal interview)
Criteria used for selection of the candidate: skills previously detailed

 

Source of information: https://emploi.cnrs.fr/Offres/Doctorant/UMR5248-CARTOK-005/Default.aspx?lang=EN

To apply for this job : https://emploi.cnrs.fr/Candidat/Login.aspx?ReturnUrl=%2fCandidat%2fOffre%2fUMR5248-CARTOK-005%2fCandidater.aspx

Articles - Characterization of the plasticity of nuclear membranes: complementarity of MS and NMR

In order to better understand the plasticity of the nuclear membrane, a team of researchers from the Institute of Chemistry and Biology of Membranes and Nano-objects in Bordeaux and researchers from the University of the Basque Country (Bilbao, Spain) and the University of Bath (United Kingdom) worked on human liver embryonic cell membranes. Their analysis, combining mass spectrometry and NMR, made it possible to measure the elasticity of the membranes, associating it with their lipid composition. This novel approach could be an indicator in the diagnosis of pathologies related to cancer or muscular dystrophy.

In human cells, many membranes define compartments that are essential for cell life and death. In particular, the envelope of the nuclei containing DNA is composed of a lipid bilayer, the inner and outer nuclear membranes, hosting membrane proteins or attached proteins. In contrast to the outer membrane of cells, the nuclear membrane is assumed to be highly plastic, to accompany the morphological changes of the nucleus during the different phases of cell replication. This nuclear envelope presents in particular large invaginations of submicrometric size: the nuclear membrane penetrates deeply into the core of the compacted DNA, as shown in the figure below. Their role is still unknown, but their increase is linked to various dysfunctions and is often used as a marker of cancerous conditions and muscular dystrophy.

In order to better understand the plasticity of the nuclear membrane, researchers from the Institute of Chemistry and Biology of Membranes and Nanoobjects in Bordeaux and researchers from the University of the Basque Country (Bilbao, Spain) and the University of Bath (UK) have been working on the nuclear membranes of human liver embryonic cells. After isolating the nuclei from the rest of the cell by a method that did not use detergents, but a device under nitrogen pressure inducing the opening of the cells by cavitation, they purified the lipids from the 2 membranes surrounding the nuclei. An analysis combining mass spectrometry and NMR of liquids revealed an atypical lipid composition, with large quantities of phosphatidylcholines, phosphatidylinositols and cholesterol lipids and especially the presence of very many unsaturations making the membrane extremely fluid. These extracted lipids were reconstituted into vesicles and observed by NMR of solids, thanks to the French research infrastructure of very high field NMR. The spectra of these initially spherical vesicles were shown to be highly deformed under the effect of magnetic fields, a phenomenon not usually observed with lipid vesicles from the plasma membrane or other cellular compartments. Using an adapted physical theory, the researchers related the deformation of the spectra to the deformation of the vesicles into ellipsoid ellipsoids of revolution, of the prolate type, with a membrane elasticity 100 times greater than that of the plasma membrane surrounding the cells, explaining their deformation by magnetic fields. Researchers have associated this property with the particular lipid composition of nuclear membranes and in particular with the high rate of establishment of aliphatic lipid chains. This new and relatively simple method of measuring the elasticity of membranes, by associating it with their lipid composition, opens up a new field for characterising the plasticity of membranes which could be affected in particular during pathologies.

 

Image
© E.Dufourc

 

 

Figure legend: Left: Human liver embryonic cells, blue (DNA), green (Membranes). The arrow shows the invagination of the membrane in the DNA (10 µm scale). Right: NMR spectrum of phosphorus solids of lipids extracted from the nuclear membrane, reconstituted as micrometric vesicles, and diagram illustrating their deformation into ellipsoid of prolate revolution under the effect of a magnetic field.

 

 

 

 

Références :

Dazzoni R, Grélard A, Morvan E, Bouter A, Applebee CJ, Loquet A, Larijani B, Dufourc EJ. The unprecedented membrane deformation of the human nuclear envelope, in a magnetic field, indicates formation of nuclear membrane invaginations. Sci Rep. 2020 Mar 20;10(1):5147. [PubMed]

Dazzoni R, Buré C, Morvan E, Grélard A, Gounou C, Schmitter JM, Loquet A, Larijani B, Dufourc EJ. Tandem NMR and Mass Spectrometry Analysis of Human Nuclear Membrane Lipids. Anal Chem. 2020 May 6. [PubMed]

 

Contacts : 

Erick Dufourc, 
Institute of Chemistry and Biology of Membranes and Nano-objects (CBMN)
e.dufourc@cbmn.u-bordeaux

Banafshe Larijani
University of Bath (UK)
bl666@bath.ac.uk

Stéphanie Younès
Communication Manager - CNRS Institute of Chemistry
inc.communication@cnrs.fr

Source : https://www.inc.cnrs.fr/fr/cnrsinfo/diagnostic-une-methode-rmn-pour-caracteriser-la-plasticite-des-membranes-nucleaires

COVID-19

Covid-19Due to the current health situation, sample preparation and mass spectrometry analysis is suspended. The time taken to return the results is consequently longer. The Platform's staff is working hard to limit the impact of the current crisis on your projects. All of the members of the Platform remain mobilized to exchange with you on current and future projects.

Corinne Buré, visiting researcher at the University of Texas, Austin, USA - Second stay

From August 19, 2019 to February 18, 2020: Corinne Buré spent a second scientific stay in the laboratory of Jennifer Brodbelt, Professor at the University of Texas, Austin, USA. This second experience was accomplished thanks to a Fulbright fellowship. Corinne tells us about her experience:

"Lipopolysaccharides (LPS) are the outer membrane constituents of gram-negative bacteria (Pseudomonas aeruginosa) and play a very important role in the formation of biofilms involved in public health problems. In order to fight against biofilms and to understand the mechanisms involved, it is necessary to study the structure of these LPS made up of lipid A and polysaccharide chains. Currently, these molecules are analyzed in mass spectrometry using classical fragmentation, which does not always generate enough fragment ions to characterize their structure. Ultraviolet photodissociation (UVPD) is a very innovative mass spectrometry fragmentation technique that can generate many fragment ions complementary to the classical techniques. This technique is not yet widely used in laboratories. The aim of this Fulbright mobility project was to acquire expertise (use of UVPD and data interpretation) in a precursor laboratory and to apply it to a model strain of Pseudomonas aeruginosa (PAO1) and ten strains of cystic fibrosis patients. Indeed, Jennifer Brodbelt's group (University of Texas at Austin) is a precursor laboratory and is essential for this type of study. For many years, her group has been modifying mass spectrometers with "home-made" UVPD and has demonstrated the effectiveness of this technique on various molecules including LPS.

During these 6 months, I was able to analyze the LPS and lipid A (part of LPS) of the different strains studied with different modes of fragmentation. The results of these experimental data are still being processed. However, it appears that new lipid A could be characterized in the model strain thanks to, among other things, UVPD fragmentation. Further promising results on the characterization of LPS are in progress."

Thanks to the Fulbright fellowship and the 6-month stay, a solid collaboration was established. A publication is currently being written and the experiences can be continued in the future, in particular with the exchange of students between the two universities.

Contact : corinne.bure@u-bordeaux.fr

 

Lumos
Orbitrap Fusion Lumos with home-made Ultraviolet Photodissociation.

 

 

Photo 2019
Last lunch time with Professor Jennifer Brodbelt's entire research group, february 2020.