This is the website of the Carlos Ibanez lab at the Karolinska Institute. In this page, we post the latest news from the KI lab. Make sure to visit the different sections of the site for more information. If you were redirected to this page from our older address, please bookmark the new address carlosibanezlab.se for future use.
Work at our laboratory focuses on understanding the functions and signaling mechanisms of neuronal growth factors in neural development, injury responses and metabolic regulation, for the development of better therapies to diseases of the nervous system and metabolism.
Postdoctoral fellows are currently being recruited to the laboratory. We are seeking talented, innovative and enthusiastic researchers with a PhD awarded within the last 10 years. Candidates with expertise in neurobiology, metabolism and mouse genetics are encouraged to apply.
Applications, including CV, list of publications and statement of future interests should be sent to Prof. Carlos Ibanez . Applicants should arrange to have at least two confidential letters of reference sent independently by referees to this email address.
Funding is available for an initial period of 2 to 3 years, starting any time during 2013.
Deadline for application is March 31, 2013.
Cold Spring Harbour Perspectives in Biology has published Carlos Ibanez’s review on the structure and physiology of the RET receptor tyrosine kinase as part of their collection of reviews on receptor tyrosine kinases. RET, GDNF family ligands, and GFRα coreceptors activate signaling pathways involved in kidney and nervous system development. RET mutations cause Hirschsprung’s disease and at least four cancers. Read the full paper HERE.
Cell Reports publishes today our latest paper describing a structure-function map of the death domain of the p75 neurotrophin receptor (Charalampopoulos et al. 2012)
Structural determinants underlying signaling specificity in the tumor necrosis factor receptor superfamily (TNFRSF) are poorly characterized and it is unclear whether different signaling outputs can be genetically dissociated. The p75 neurotrophin receptor (p75NTR), also known as TNFRSF16, is a key regulator of trophic and injury responses in the nervous system. In this paper, we describe a genetic approach to dissect p75NTR signaling and decipher its underlying logic. Structural determinants important for regulation of cell death, NF-kB and RhoA pathways were identified in the p75NTR death domain. Pro-apoptotic and pro-survival pathways mapped onto non-overlapping epitopes, demonstrating that different signaling outputs can be genetically separated in p75NTR. Dissociation of JNK and caspase-3 activities indicated that JNK is necessary but not sufficient for p75NTR-mediated cell death. RIP2 recruitment and RhoGDI release were mechanistically linked, indicating that competition for DD binding underlies cross-talk between NF-kB and RhoA pathways in p75NTR signaling. These results provide new insights into the logic of p75NTR signaling and pave the way for a genetic dissection of p75NTR function and physiology.
Read the full paper HERE.
The Knut and Alice Wallenberg Foundation has today appointed Carlos Ibanez as a Wallenberg Scholar. The award includes a research grant of 15 million Swedish crowns over 5 years. Quote from the Foundation’s website: “The Foundation’s purpose is to support Swedish research and thereby strengthen Sweden as a research nation. Since 2009, we have appointed a total of 46 Wallenberg Scholars. The appointed researchers all belong to the international research forefornt in all areas of science, with an emphasis on medicine and the natural sciences, says Peter Wallenberg Jr., vice chairman of the Knut and Alice Wallenberg Foundation.” Read the text of the announcement (in Swedish) HERE and press release from Karolinska Institute HERE.
The Journal of Neuroscience publishes today our paper on the role of the GDNF receptor GFRa1 in the main olfactory system (Marks et al. 2012). In this work, we investigated the consequences of GFRα1 deficiency for mouse olfactory system development and function.
GDNF and its receptor GFRα1 are prominently expressed in the olfactory epithelium (OE) and olfactory bulb (OB), but their importance for olfactory system development has been unknown. In the OE, we found that GFRα1 was expressed in basal precursors, immature olfactory sensory neurons (OSNs), and olfactory ensheathing cells (OECs), but was excluded from mature OSNs. The OE of newborn Gfra1 knock-out mice was thinner and contained fewer OSNs, but more dividing precursors, suggesting deficient neurogenesis. Immature OSN axon bundles were enlarged and associated OECs increased, indicating impaired migration of OECs and OSN axons. In the OB, GFRα1 was expressed in immature OSN axons and OECs of the nerve layer, as well as mitral and tufted cells, but was excluded from GABAergic interneurons. In newborn knock-outs, the nerve layer was dramatically reduced, exhibiting fewer axons and OECs. Bulbs were smaller and presented fewer and disorganized glomeruli and a significant reduction in mitral cells. Numbers of tyrosine hydroxylase-, calbindin-, and calretinin-expressing interneurons were also reduced in newborn mice lacking Gfra1. At birth, the OE and OB of Gdnf knock-out mice displayed comparable phenotypes. Similar deficits were also found in adult heterozygous Gfra1+/− mutants, which in addition displayed diminished responses in behavioral tests of olfactory function. We conclude that GFRα1 is critical for the development and function of the main olfactory system, contributing to the development and allocation of all major classes of neurons and glial cells.
Read the full paper HERE.
PhD student Carolyn Marks nailed her thesis at the KI library this week. Tradition obliges, and the golden nail went into the wooden slab one more time.
The event marks the final count-down for her thesis defense, to take place on December 7. Attracted by the prospect of champagne and refreshments, fellow lab mates joined in for the occassion.
Photograph by postdoc fellow Tingqing Guo.
Starting in the Fall of 2012, a new laboratory dedicated to neurotrophic factor research will be established at the Life Sciences Institute (Neurobiology Programme) of the National University of Singapore. The research actitivies of the NUS lab will run in parallel to and complement with those ongoing at the KI lab. The initial focus of the NUS group will be on genetic studies of death receptor signaling and physiology, as well as the identification of novel, mechanism-based receptor inhibitors. Follow developments in the NUS lab at carlosibanezlab.se/NUS.
PhD student Carolyn Marks is set to defend her thesis, entitled “Regulatory mechanisms in olfactory system assembly and function”, on December 7, 2012. Her external examiner will be Professor Charles Greer from Yale University. Faculty members in the thesis committee will be Professors Ole Kiehn (KI), Jonas Muhr (KI), Tibor Harkany (KI) and Anders Lansner (KTH). Watch this space for updates on thesis nailing and other rituals.
The FASEB Journal has published our paper on the role of the activin receptor ALK7 in the control of female reproduction (Sandoval-Guzman et al. 2012). In this work, we investigated the expression and function of the activin receptor ALK7 in the female reproductive axis using Alk7-knockout mice.
Alk7-knockout females showed delayed onset of puberty and abnormal estrous cyclicity, had abnormal diestrous levels of FSH and LH in serum, and their ovaries showed premature depletion of follicles, oocyte degeneration, and impaired responses to exogenous gonadotropins. In the arcuate nucleus, mutant mice showed reduced expression of Npy mRNA and lower numbers of Npy-expressing neurons than wild- type controls. Alk7 knockouts showed a selective loss of arcuate NPY/AgRP innervation in the medial preoptic area, a key central regulator of reproduction. These results indicate that ALK7 is an important regulator of female reproductive function and reveal a new role for activin signaling in the control of hypothalamic gene expression and wiring. Alk7 gene variants may contribute to female reproductive disorders in humans, such as polycystic ovary syndrome.
Read the full paper HERE.
Karima Mezghenna obtained a PhD in Biology and Health Sciences at Montpellier 1 University under the direction of Prof. Anne-Dominique Lajoix with the title ”Role of pancreatic and muscular neuronal NO synthases in the pathogenesis of prediabetic states”. Her work focused on unraveling compensatory mechanisms involved in insulin hypersecretion in insulin resistant rats with a special interest in the nitric oxide pathway. Karima will be joining our metabolism team in October to study the role of activin signaling through Alk7 and Alk4 in islet biology and the control of glucose homeostasis.