PhD application open at the IPHC-CNRS (Strasbourg)

ARE BIRDS DEMIGODS OF GLYCATION RESISTANCE?
Key-words : high-sugar diet, glycation, adaptation, evolutionary biology, proteomics, birds

Birds are both hyperglycemic, with blood sugar levels that are diabetic-like in mammals, and are unusually long-lived, with tiny hummingbirds living more than 10 years in the wild. Glycation stress, and the accumulation of Advanced Glycation Endproducts (AGEs), is widely associated with senescence and aging, though long-lived birds, with their elevated metabolism, seem a paradoxical exception to this rule. Our team will leverage its multidisciplinary expertise in evolutionary biology, ecophysiology, and analytical chemistry to explore: (i) how glucose stress and life history traits vary among bird orders; (ii) what traits underlie the abilities of two avian species at opposite ends of the energetics and lifespan spectrum to resist or mitigate the effects of hyperglycemia; and (iii) the molecular mechanisms conferring protection to birds from the adverse effects of glycation stress and the accumulation of AGEs.
Preliminary proteomics data has already been collected in support of the third goal above. The results of this project will open new avenues for investigating the fundamental links between glycation stress, metabolism, and aging that apply to all animals, including shedding insights into related pathologies in humans and model mammalian systems.
The PhD candidate will have: (Part 1) to obtain an accurate proteomic assessment of glycation stress in two bird species, the zebra finch (Taeniopigya guttata) and the ruby-throated hummingbird (Archilocus colibris) and (Part 2) to detect specific anti-AGEs proteins that may be up-regulated in response to an experimental short-term exposition to high-AGEs diet in zebra finches, and whether proteomic profiles of putative anti-glycation pathways are modulated in hummingbirds over age.

Anticipated results: the present application will provide the scientific community with accurate methodology to assess glycation in birds, as well as with an unprecedented measurement of putative mechanisms of protection against the pro-ageing effects of glycation that may have co-evolved with birds’ exceptional longevity. It will also be the first step of our whole project addressing the nature of the mechanisms by which evolution resolved a specific environmental challenge, which may account for individual fitness variability. By combining mechanistic (anti-glycation processes) and evolutionary approaches (individual fitness assessment), we aim to open new insights into how evolution has dealt with the chemical constraints when glucose/fructose is the main energy fuel. Our complementary study design of phylogenetic and experimental approaches using individual records, allows for extensive cross-sectional and longitudinal tests. Crosschecking the data provided by those approaches will yield highlight under which evolutionary/environmental conditions protections against glycation have evolved and will hopefully help us to better deal with specific human health questioning.

The IPHC will commit in the project their state-to-the-art equipment in proteomics (the IPHC-DSA is part of the National Infrastructure of proteomic (ProFI, http://www.profiproteomics.fr/) and their technical platforms applying molecular biology and mass spectrometry to evolutionary biology questions (IPHC-DEPE, http:// www.iphc.cnrs.fr/-Supports-techniques-.html). The project will also beneficiate from the unique expertise of an external collaborating team of the University of Toronto,
leaded by Dr K. Welch, a recognized specialist of hummingbirds’ metabolism (https://www.welchbiology.com/fr/welch-lab-page-daccueil/). Hummingbirds are housed at the UTSC Vivarium (the Welch lab has maintained captive birds for 10+ years). They will perform all live hummingbird procedures, including complementary analyses of rates of glucose and fructose uptake and utilization using a combination of 13C‐isotope tracer techniques and respirometry. They will also sacrifice and sample tissues from birds and prepare these for “omic” and chemical analyses.

Expected skills: The PhD candidate will be shared by two departments of the IPHC: Ecology, Physiology and Ethology, and the Analytical Sciences departments. He will run experiments on zebra finches and lab analysis at the DEPE, and be initiated and do part of the analyses in proteomics at the DSA. We are seeking a candidate interested in developing an ecophysiology and evolutionary biology approach of sugar metabolism, and how evolution has found perennial solutions to a pathological issue for humans. To do so, he/she will need to have interest/background in laboratory work (biochemistry, molecular biology), and in whole-organism approach (being confident with manipulating living birds). A strong background in statistics (mixed models, Multivariate analysis, R coding) is also needed.

Acquired expertise: The PhD candidate will become an expert in:
– Metabolism as a mechanism sustaining avian evolution of life history traits
– Mechanistic approach of evolutionary biology
– Statistics
– Ecophysiology
– Evolution of ageing
He/she will be trained at different degrees to:
– Biochemistry and molecular biology
– Proteomics and statistical analysis of large datasets.

Key words: Ecophysiology, Biochemistry, Proteomics, Birds

Application: The project is not presently funded and we are seeking for a Master II student who wants to apply for a PhD at the doctoral school ED 414 of the University of Strasbourg (first week of July in Strasbourg, https://www.unistra.fr/index.php?id=18138). Being in the first half of the Master and having a mean mark of >14/20 will be necessary to be pre-selected for the interview of the doctoral school. The selection of applications take place around the 24th of June, and so rank and marks are needed at that time. If successful, the PhD contract will be provided by the University of Strasbourg, with a PhD allowance of ca. 1700 euros (before taxes) per month for three years (2020-2023), starting next October. The PhD contract will provide access to the French social security. Possibilities of teaching at the University of Strasbourg are open, with substantial income gain. The PhD will be hosted by the doctoral school of the University of Strasbourg (ED 414), and then will have to fulfil all the training obligatory for each PhD (54h in total), mostly provided by the University (French lessons, animal care training, animal ethics…). The IPHC research teams are friendly and international and non-French speaking applicants are welcome.

Contacts: Fabrice Bertile, IPHC-CNRS, [email protected], http://www.iphc.cnrs.fr/-Spectrometrie-de-Masse-BioOrganique-LSMBO-.html
François Criscuolo, IPHC-CNRS, [email protected], http://www.iphc.cnrs.fr/-Ethologie-et-Physiologie-Evolutive-EPE-.html

Deadline: 30 May 2020 for applications. A short list of 5 applicants will be established shortly and interviews by IPHC realized in the first 15 days of June.

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