Tag Archives: homeostasis

Postdoctoral Research Fellow in Iron Biology – IRSD Toulouse, France

A postdoctoral research fellow position is available for 3 years in the Delphine Meynard research group (http://en.irsd.fr/team-4-genetics-and-regulation-of-iron-metabolism.html).  We are part of the Digestive Health Research Institute (IRSD) in Toulouse in France. Toulouse is a dynamic research area located in south of France that comprises many internationally recognized laboratories and gives access to a network of high-level skills research platforms in life sciences (fundamental biology, agronomy, environment, health) making possible almost all research projects.

The Digestive Health Research Institute accredited by INSERM, INRA, ENVT and Toulouse University, is internationally recognized and offerins a productive scientific environment centered on basic and clinical research to understand and treat diseases of the intestine and the liver. IRSD brings together a total of >80 researchers, professors, technicians, students and post-docs of different nationalities.

Our research focuses on iron metabolism and its disturbance in human diseases. Our lab is a dynamic team of scientists, MD, graduate students, and technicians. Our main goal is to characterize the regulation of iron homeostasis at the cellular and molecular levels and to develop new therapeutic strategies for the treatment of iron related disorders. The postdoctoral project will specifically address the role of proteases in the regulation of iron homeostasis and develop new strategies to target those proteases. The postdoctoral fellow will use several approaches including molecular and cellular biology, animal models, and biochemistry but also techniques related to proteases such as enzymatic activity assay, activity based probes, and in situ zymography.

Applicants for this position must have a Ph.D. in the biochemical sciences. A suitable candidate will have a proven track record of research accomplishments including first author publications in international peer-reviewed journals and excellent experience in: molecular and cellular biology, biochemistry, mouse models. Skills with proteases would be appreciable. In addition, excellent communication/interpersonal skills are required.

Please email a cover letter, CV, and two letters of support from former mentors or collaborators (including their contact information) to Delphine Meynard: delphine.meynard@inserm.fr

Matriptase-2 Deficiency Protects From Obesity by Modulating Iron Homeostasis

Folgueras AR, Freitas-Rodríguez S, Ramsay AJ, Garabaya C, Rodríguez F, Velasco G, López-Otín C. Nat Commun. 2018 Apr 10;9(1):1350 PDF

Commentary by Dr Gautam Rishi and Prof Nathan Subramaniam Liver Disease and Iron Disorders Research Group, Queensland University of Technology, Brisbane.

Iron dysfunction is associated with many clinical conditions including neurodegenerative disorders, cancers, the anemia associated with chronic disease, and many iron disorders. Several studies have also linked disturbed iron regulation with metabolic disorders including obesity; however in most cases it is linked to iron deficiency, with chronic inflammation identified as a possible cause. The iron regulatory hormone hepcidin is regulated by a number of proteins and various stimuli. Matriptase-2, encoded by TMPRSS6, is thought to be a repressor of hepcidin expression through its cleavage of the positive regulator, hemojuvelin (encoded by HJV). A deficiency of matriptase-2 in humans is associated with a form of anemia termed iron-refractory iron deficiency anemia (IRIDA).

This study by Folgueras et al, from the laboratory of Prof Carlos Lopez-Otin, demonstrates that mice with deficiency of matriptase-2 are protected from obesity induced by a high-fat diet. The authors demonstrate, and ascribe this protective effect to the increased breakdown of fat/lipids in matriptase-2 deficient mice resulting in decreased fat deposition. Surprisingly, the authors observed decreased levels of the “hunger hormone” leptin and a concomitant increase in food intake in matriptase-2 knockout mice which however showed decreased weight gain. Matriptase-2 knockout mice fed a high fat diet also had decreased liver steatosis and improved glucose tolerance. Decreasing hepcidin expression in matriptase-2 knockout mice through use of a neutralizing antibody against HJV reversed these effects. In summary these exciting studies demonstrate an important role for hepcidin and thus iron regulation in lipid homeostasis and function of adipocytes, opening new avenues in the fight against obesity.