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Singapore media highlights identification of small molecule targeting the transmembrane domain of death receptor p75NTR

The Saturday edition of the The Straits Times publishes today an interview with Carlos Ibanez highlighting the identification a small molecule targeting the transmembrane domain of death receptor p75NTR that induces melanoma cell death and reduces tumor growth (reported in our paper published in Cell Chemical Biology). Read the full article here. Also newspaper Lianhe Zaobao (Chinese Daily) carried a story (in Chinese) on the discovery.

New paper reports the identification of a small molecule targeting the transmembrane domain of death receptor p75NTR

In this new paper, we have used a novel chemical biology approach to identify a small molecule targeting the transmembrane domain of death receptor p75NTR that induces melanoma cell death and reduces tumor growth

Small molecules offer powerful ways to alter protein function. However, most proteins in the human proteome lack small-molecule probes, including the large class of non-catalytic transmembrane receptors, such as death receptors. We hypothesized that small molecules targeting the interfaces between transmembrane domains (TMDs) in receptor complexes may induce conformational changes that alter receptor function. Applying this concept in a screening assay, we identified a compound targeting the TMD of death receptor p75NTR that induced profound conformational changes and receptor activity. The compound triggered apoptotic cell death dependent on p75NTR and JNK activity in neurons and melanoma cells, and inhibited tumor growth in a melanoma mouse model. Due to their small size and crucial role in receptor activation, TMDs represent attractive targets for small-molecule manipulation of receptor function.

The paper has just been published in Cell Chemical Biology.

Read the full paper HERE.

New paper shows how RIP2 and TRAF6 compete for binding to p75NTR and regulate neuronal cell death

In this new paper, we show how intracellular effectors RIP2 and TRAF6 compete for binding to the p75NTR intracellular domain to regulate cell death of cerebellar granule neurons.

Cerebellar granule neurons (CGNs) undergo programmed cell death during the first postnatal week of mouse development, coincident with sustained expression of the death receptor p75NTR. Although ablation of p75NTR did not affect CGN cell death, deletion of the downstream effector RIP2 significantly increased CGN apoptosis, resulting in reduced adult CGN number and impaired behaviors associated with cerebellar function. Remarkably, CGN death was restored to basal levels when p75NTR is deleted in RIP2-deficient mice. We found that RIP2 gates the signaling output of p75NTR by competing with TRAF6 for binding to the receptor intracellular domain. In CGNs lacking RIP2, more TRAF6 was associated with p75NTR, leading to increased JNK-dependent apoptosis. In agreement with this, pharmacological inhibition or genetic ablation of TRAF6 restored cell death levels in CGNs lacking RIP2. These results revealed an unexpected mechanism controlling CGN number and highlight how competitive interactions govern the logic of death receptor function.

The paper has just been published in Cell Reports.

Read the full paper HERE.

New paper reveals cell-autonomous role of GFRα1 in the development of olfactory bulb GABAergic interneurons

In this new paper, we show how the GDNF receptor GFRα1 functions cell-autonomously in subpopulations of olfactory bulb interneuron precursors to regulate their generation and allocation in the mammalian olfactory bulb.

GFRα1, a receptor for glial cell line-derived neurotrophic factor (GDNF), is critical for the development of the main olfactory system. The olfactory bulb (OB) of Gfra1 knockout mice showed significant reductions in the number of olfactory sensory neurons, mitral and tufted cells, as well as all major classes of OB GABAergic interneurons. However, the latter did not express significant levels of GFRα1, leaving the mechanism of action of GFRα1 in OB interneuron development unexplained. We have found that GFRα1 is highly expressed in the precursor cells that give rise to all major classes of OB interneurons, but is downregulated as these neurons mature. Conditional ablation of GFRα1 in embryonic GABAergic cells recapitulated the cell losses observed in global Gfra1 knockouts at birth. GFRα1 was also required for the sustained generation and allocation of OB interneurons in adulthood. Conditional loss of GFRα1 altered the migratory behaviour of neuroblasts along the rostral migratory stream (RMS) as well as RMS glial tunnel formation. Together, these data indicate that GFRα1 functions cell-autonomously in subpopulations of OB interneuron precursors to regulate their generation and allocation in the mammalian OB.

The paper has just been published in Biology Open.

Read the full paper HERE.

Carlos Ibanez lab moves to the new Biomedicum building

Today is the big day. After many years of planning and construction, all the preclinical departments of Karolinska Institute move into a huge, brand-new building called BIOMEDICUM. Very handsome on the inside, less so on the outside. We are just hoping for a smooth transition.

Carlos Ibanez presents the Nobel Prize in Physiology or Medicine 2017

Presentation Speech by Professor Carlos Ibáñez, Member of the Nobel Assembly at the Karolinska Institute, Member of the Nobel Committee for Physiology or Medicine, at the award ceremony of the Nobel Prize, 10 December 2017.

New postdoc fellow joins KI group to study roles of p75NTR signaling in neuron survival and differentiation

Shounak Baksi obtained his PhD at the University of Calcutta, India, in September 2009. His thesis work focused on studies of alterations in Growth Factor Receptor Protein Binding Protein 2 (Grb2) signaling in Huntington’s disease cell model. His postdoctoral studies in Case Western Reserve University, Cleveland, OH, under the direction of Dr. Neena Singh,  focused on the role of Parkinson’s disease protein alpha synuclein in retinal and brain iron homeostasis. Shounak established the role of alpha synuclein in the process of transferrin receptor endocytosis. Shounak joins the KI team to pursue studies of p75 signaling mutant mice.

Change of Department affiliation

Carlos Ibanez’s team is now under the Department of Cell and Molecular Biology (CMB) of Karolinska Institute. Although the group was since 1996 under the Department of Neuroscience, its laboratories were already located at CMB space since 2004. This administrative change completes the integration of the Ibanez team in the CMB organization, in preparation for the big move to the new Biomedicum building next year.

New paper reveals how GDNF controls survival of molecular layer interneurons in the cerebellum

In this new paper, we show how the GDNF regulates survival of molecular layer interneurons in the cerebellum to control normal cerebellar motor learning. The paper has just been published in Cell Reports.

The role of neurotrophic factors as endogenous survival proteins for brain neurons remains contentious. In the cerebellum, the signals controlling survival of molecular layer interneurons (MLIs) are unknown, and direct evidence for the requirement of a full complement of MLIs for normal cerebellar function and motor learning has been lacking. Here, we show that Purkinje cells (PCs), the target of MLIs, express the neurotrophic factor GDNF during MLI development and survival of MLIs depends on GDNF receptors GFRα1 and RET. Conditional mutant mice lacking either receptor lose a quarter of their MLIs, resulting in compromised synaptic inhibition of PCs, increased PC firing frequency, and abnormal acquisition of eyeblink conditioning and vestibulo-ocular reflex performance, but not overall motor activity or coordination. These results identify an endogenous survival mechanism for MLIs and reveal the unexpected vulnerability and selective requirement of MLIs in the control of cerebellar-dependent motor learning.

Read the full paper HERE.

Open Position: Cellular Electrophysiologist

UPDATE 2017-05-29: Position still open. 

We are seeking a talented and enthusiastic researcher with expertise in cellular electrophysiology to advance investigations on the functions and mechanisms of neurotrophic signaling networks in the adult nervous system. The research entails functional assessment of neuronal circuits in the brains of mutant mice lacking different neurotrophic factor receptors in specific subpopulations of neurons.

Candidates will be accepted at the postdoctoral level with a PhD awarded preferably within the last 5 years. Strong and documented expertise in electrophysiological methods as applied to studies of the rodent central nervous system, such as electrophysiological recordings from brain slices, is a requirement for consideration. Experience on calcium imaging would be an advantage.

The successful candidate is expected to be sufficiently independent to set up electrophysiological methods at our laboratory, including supervision of purchase, installation and maintenance of the necessary equipment.

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 3 to 4 years, starting any time during 2017.

Open Postdoctoral Position: Molecular / Cellular Neurobiologists

UPDATE 2017-05-29: The position has been filled. 

We are seeking a talented and enthusiastic researcher with expertise in molecular and cellular neurobiology to advance investigations on the functions and mechanisms of neurotrophic signaling in the nervous system. The research entails studies of death receptor signaling pathways in cell culture models as well as phenotypic characterisation of mutant mice carrying specific mutations in neurotrophic factor receptors. Please refer to our recent list of publications in this area HERE.

Candidates will be accepted at the postdoctoral level (PhD awarded within the last 5 years). Strong and documented expertise in cellular, molecular and histological methods as applied to studies of the rodent nervous system is a requirement for consideration. Experience with genetically modified mice is highly desirable. The successful candidate is expected to be sufficiently independent to formulate questions, design experiments and perform research.

Our group belongs to a network of laboratories dedicated to different aspects of neuroscience research and provides a strong environment for scientific growth and career development.

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 3 years, starting any time during 2017.

Deadline for application is March 7, 2017.

Joint retreat of KI and NUS labs in Singapore

Fellows from the KI lab flew to Singapore for a 2 day retreat with the NUS group on 16th and 17th of January 2017. After 4 years of joint lab meetings over Skype, fellows of both groups enjoyed an opportunity to discuss common projects and ideas face to face. We were joined by the NUS and UCSD groups of Prof. Ed Koo and had joint plenary and also parallel sessions, as well as group building activities, as shown in the photo below.

 

New paper shows novel function of the GFRα1 receptor

In this new paper, we show how the GFRα1 receptor regulates Purkinje cell migration independently of GDNF or RET, by limiting the function of NCAM. The paper has just been published in Cell Reports.

During embryonic development of the cerebellum, Purkinje cells (PCs) migrate away from the ventricular zone to form the PC plate. The mechanisms that regulate PC migration are incompletely understood. Here, we report that the neurotrophic receptor GFRα1 is transiently expressed in developing PCs and loss of GFRα1 delays PC migration. Neither GDNF nor RET, the canonical GFRα1 ligand and co-receptor, respectively, contribute to this process. Instead, we found that the neural cell adhesion molecule NCAM is co-expressed and directly interacts with GFRα1 in embryonic PCs. Genetic reduction of NCAM expression enhances wild-type PC migration and restores migration in Gfra1 mutants, indicating that NCAM restricts PC migration in the embryonic cerebellum. In vitro experiments indicated that GFRα1 can function both in cis and trans to counteract NCAM and promote PC migration. Collectively, our studies show that GFRα1 contributes to PC migration by limiting NCAM function.

Read the full paper HERE.

New paper shows how thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons

In our latest paper, we show how thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons. The paper has just been published in eLife.

Neocortical GABAergic interneuron migration and thalamo-cortical axon (TCA) pathfinding follow similar trajectories and timing, suggesting they may be interdependent. The mechanisms that regulate the radial dispersion of neocortical interneurons are incompletely understood. In this new study we report that disruption of TCA innervation, or TCA-derived glutamate, affected the laminar distribution of GABAergic interneurons in mouse neocortex, resulting in abnormal accumulation in deep layers of interneurons that failed to switch from tangential to radial orientation. Expression of the KCC2 cotransporter was elevated in interneurons of denervated cortex, and KCC2 deletion restored normal interneuron lamination in the absence of TCAs. Disruption of interneuron NMDA receptors or pharmacological inhibition of calpain also led to increased KCC2 expression and defective radial dispersion of interneurons. Thus, although TCAs are not required to guide the tangential migration of GABAergic interneurons, they provide crucial signals that restrict interneuron KCC2 levels, allowing coordinated neocortical invasion of TCAs and interneurons.

Read the full paper HERE. (Supplemental information 31.6MB)

Swedish Research Council awards new research grant to Carlos Ibanez Lab

The Swedish Research Council (Vetenskapsrådet) has awarded a new grant to our KI group for work on neurotrophic signaling in the adult nervous system and its importance for neuropsychiatric disorders. Tack för förtroendet!

Carlos Ibanez named Weston Visiting Professor at the Weizmann Institute of Science

The Weizmann Institute in Israel has named Carlos Ibanez Weston Visiting Professor in the Faculty of Biochemistry, Department of Biomolecular Sciences for 3 years, starting October 2016 to conduct educational and research activities.

New lab technician joins KI group to help with histology and imaging

Wei Wang has a BSc in Public Health from Medical College of Southeast University, Nanjing, China, and a MSc in Environmental Toxicology from Shanghai Medical College, Fudan University, Shanghai, China. She has worked as Assistant Researcher at the Shanghai Institute of Applied Physics, Shanghai Institutes for Biological Sciences and the University of Gothenburg in Sweden. She joins our group to assist with histological methods and imaging of tissue samples from our mouse models.

New paper demonstrates requirement of p75NTR death domain and transmembrane cysteine for neuronal death in the CNS

In our latest paper, we show how dimers of the p75NTR neurotrophin receptor are indipensable for p75NTR-mediated cell death in the central nervous system. The paper has just been published in the Journal of Neuroscience.

The oligomeric state and activation mechanism that enable p75 NTR to mediate these effects have recently been called into question. In this new study, we have investigated mutant mice lacking the p75NTR death domain (DD) or a highly conserved transmembrane (TM) cysteine residue (Cys 259) implicated in receptor dimerization and activation. Neuronal death induced by proneurotrophins or epileptic seizures was assessed and compared with responses in p75NTR knock-out mice and wild-type animals. Proneurotrophins induced apoptosis of cultured hippocampal and cortical neurons from wild-type mice, but mutant neurons lacking p75NTR, only the p75NTR DD, or just Cys259 were all equally resistant to proneurotrophin-induced neuronal death. Homo-FRET anisotropy experiments demonstrated that both NGF and proNGF induce conformational changes in p75 NTR that are dependent on the TM cysteine. In vivo, neuronal death induced by pilocarpine-mediated seizures was significantly reduced in the hippocampus and somatosensory, piriform, and entorhinal cortices of all three strains of p75 NTR mutant mice. Interestingly, the levels of protection observed in mice lacking the DD or only Cys 259 were identical to those of p75 NTR knock-out mice even though the Cys 259 mutant differed from the wild-type receptor in only one amino acid residue. We conclude that, both in vitro and in vivo, neuronal death induced by p75NTR requires the DD and TM Cys259, supporting the physiological relevance of DD signaling by disulfide-linked dimers of p75NTR in the CNS.

Read the full paper HERE.

Open position: Laboratory technician - Histology

UPDATE 2016-05-25: The position has been filled. 

We are seeking a laboratory technician to help us with histological studies of our lines of mutant mice. The candidates should have documented expertise in histological techniques, including tissue sectioning, immunohistochemistry and microscopy. Experience in histological analysis of nervous tissue is preferred. This is a project employment for a period of up to 2 years.

Application, including CV and reference names of two latest project supervisors should be sent to Prof. Carlos Ibanez

Deadline for application is 29th April, 2016

New review article published: Biology of GDNF and its receptors — Relevance for disorders of the central nervous system

A targeted effort to identify novel neurotrophic factors for midbrain dopaminergic neurons resulted in the isolation of GDNF (glial cell line-derived neurotrophic factor) from the supernatant of a rat glial cell line in 1993. Over two decades and 1200 papers later, the GDNF ligand family and their different receptor systems are now recognized as one of the major neurotrophic networks in the nervous system, important for the devel- opment, maintenance and function of a variety of neurons and glial cells. The many ways in which the four mem- bers of the GDNF ligand family can signal and function allow these factors to take part in the control of multiple types of processes, from neuronal survival to axon guidance and synapse formation in the developing nervous system, to synaptic function and regenerative responses in the adult. In this review, recently published in Neurobiology Of Disease, basic aspects of GDNF signaling mechanisms and receptor systems are first summarized followed by a review of current knowledge on the physiology of GDNF activities in the central nervous system, with an eye to its relevance for neurodegenerative and neuropsychiatric diseases. Read the full paper HERE.

New paper describes first structures of protein complexes of the p75NTR death domain

Our latest paper describes new NMR structures of the death domain in complex with downstream interactions RhoGDI and RIP2 as well as the death domain dimer. These are the first structural insights into p75NTR signaling and reveal many surprises for the death domain superfamily. The paper is now available online at eLife

Death domains (DDs) mediate assembly of oligomeric complexes for activation of downstream signaling pathways through incompletely understood mechanisms. We report structures of complexes formed by the DD of p75 neurotrophin receptor (p75NTR) with RhoGDI, for activation of the RhoA pathway, with caspase recruitment domain (CARD) of RIP2 kinase, for activation of the NF-kB pathway, and with itself, revealing how DD dimerization controls access of intracellular effectors to the receptor. RIP2 CARD and RhoGDI bind to p75NTR DD at partially overlapping epitopes with over 100-fold difference in affinity, revealing the mechanism by which RIP2 recruitment displaces RhoGDI upon ligand binding. The p75NTR DD forms non-covalent, low-affinity symmetric dimers in solution. The dimer interface overlaps with RIP2 CARD but not RhoGDI binding sites, supporting a model of receptor activation triggered by separation of DDs. These structures reveal how competitive protein-protein interactions orchestrate the hierarchical activation of downstream pathways in non-catalytic receptors.

Cancerfonden awards new research grant to Carlos Ibanez Lab

The Swedish Cancer Society (Cancerfonden) has awarded a new grant to our KI group for work on ALK7, p75 and GDNF signalling and biology. Tack för förtroendet!

Carlos Ibanez named Visiting Professor at the University of Palermo

The University of Palermo in Italy has named Carlos Ibanez  Visiting Professor at the Department of Experimental Biomedicine and Clinical Neuroscience, starting September 2015 to participate in research and didactic activities.

Mechanism for neuron-type-specific signaling by the p75NTR death receptor unravelled

In our latest paper, we show that the p75 neurotrophin receptor p75NTR can signal very differently in diferent types of neurons. Using pharmacological and genetic techniques, we demonstrate that this is partly controlled by differential proteolytic cleavage of the receptor in different cell types. The new work has appeared online in the Journal of Cell Science

Signaling by the p75 neurotrophin receptor (p75NTR) is often referred to as cell-context dependent, but neuron-type specific signaling by p75NTR has not been systematically investigated. Here, we report that p75NTR signals very differently in hippocampal neurons (HCNs) and cerebellar granule neurons (CGNs), and present evidence indicating that this is partly controlled by differential proteolytic cleavage. NGF induced caspase-3 activity and cell death in HCNs but not in CGNs, while it stimulated NFκB activity in CGNs but not in HCNs. HCNs and CGNs displayed different patterns of p75NTRproteolytic cleavage. While the p75NTR carboxy terminal fragment (CTF) was more abundant than the intracellular domain (ICD) in HCNs, CGNs exhibited fully processed ICD with very little CTF. Pharmacological or genetic blockade of p75NTR cleavage by gamma-secretase abolished NGF-induced upregulation of NFκB activity and enabled induction of CGN death, phenocopying the functional profile of HCNs. Thus, the activities of multifunctional receptors, such as p75NTR, can be tuned into narrower activity profiles by cell-type-specific differences in intracellular processes, such as proteolytic cleavage, leading to very different biological outcomes. Read the full article HERE.

And here we are...

Ibanez-lab_2015

Left: Annika, Sabrina, Maritina, Karima, Nuria, Favio
Right: Lilian, Christina, Diana, Patricia, Petronella, Claire

New method for topographic transcriptome mapping of the mouse brain

In our latest paper, we demonstrate that spatially resolved RNA-seq is ideally suited for high resolution topographical mapping of genome-wide gene expression in heterogeneous anatomical structures such as the mammalian central nervous system. The work has  appeared online in Genome Biology

Cortical interneurons originating from the medial ganglionic eminence, MGE, are among the most diverse cells within the CNS. Different pools of proliferating progenitor cells are thought to exist in the ventricular zone of the MGE, but whether the underlying subventricular and mantle regions of the MGE are spatially patterned has not yet been addressed. In this work, we combined laser-capture microdissection and multiplex RNA-sequencing to map the transcriptome of MGE cells at a spatial resolution of 50 microns. Distinct groups of progenitor cells showing different stages of interneuron maturation were identified and topographically mapped based on their genome-wide transcriptional pattern. Although proliferating potential decreased rather abruptly outside the ventricular zone, a ventro-lateral gradient of increasing migratory capacity was identified, revealing heterogeneous cell populations within this neurogenic structure. Read the full article HERE.

Two new postdoc fellows join KI group to study roles of growth factor receptors in neuron differentiation, survival and function

Favio Krapacher obtained his PhD at the Universidad Nacional de Córdoba, Argentina, in December 2013. His thesis work focused on studies of p35 transgenic mice as a model of attention deficit hyperactivity disorder, and included a series of behavioral, pharmacological and biochemical studies. Favio joins the KI team to study the role of Alk4 signaling in controlling the differentiation and migration of specific subtypes of forebrain GABAergic interneurons.

Nuria Gresa-Arribas obtained her PhD at the Universiy of Barcelona, Spain, in 2011. Her thesis examined the neurotoxic role of pro-inflammatory microglial cells and the role of C/EBPs transcription factors. She later worked as postdoctoral fellow under the direction of Dr. Josep Dalmau at the same university for studies of autoimmune neurologic diseases associated with antibodies to neuronal cell surface or synaptic proteins. Nuria will join the KI team in November to pursue studies of p75 signaling mutant mice.

Research Assistant joins KI group to help with mouse genotyping

Petronella Johansson trained at Kristianstad Highschool and subsequently pursued doctoral studies at the Scottish Fish Immunology Research Centre, University of Aberdeen, United Kingdom, where she obtained a PhD in 2014. Petronella joins our group to help with mouse breeding and genotyping, as well as molecular techniques and admin duties.

New discovery explains how ALK7 receptor regulates fat accumulation in obesity

In our latest paper, we report that the sensitivity of fat cells to signals that increase the breakdown of fat is linked to the receptor ALK7. The discovery, which is published in eLife, suggests that ALK7 is an interesting target for future strategies to treat obesity.

The ALK7 receptor is predominantly found in fat cells and tissues involved in controlling the metabolism. Intriguingly, mice with a mutation in ALK7 accumulate less fat than mice with a functional version of the protein. Until now, it has not been known why.

We created mice whose fat cells lack ALK7, but whose other cells all produce ALK7 as normal. We found that fat cells lacking the ALK7 receptor are more sensitive to adrenaline and noradrenaline signals, a finding that can explain why they accumulate less fat even though the mice were on a high-fat diet. Adrenaline and noradrenaline are central players in metabolism. These hormones trigger the burst of energy and increase in heart rate and blood pressure that are needed for the “fight-or-flight” response. The hormones normally stimulate the breakdown of fat, but when nutrients are plentiful, fat cells become resistant to this signal and instead store fat. This mechanism evolved to facilitate energy storage during times of abundant food supply, enhancing survival upon starvation. In the industrialized world where food is constantly accessible, this resistance can cause an unhealthy increase in body fat and result in obesity.

We then investigated if it is possible to prevent obesity by blocking ALK7. At present, there are no known ALK7 inhibitors, but we solved this by generating mice with a special mutation in ALK7 which renders it sensitive to inhibition by a chemical substance. This made it possible for us to block the receptor at any time in an otherwise normal adult animal.

Using this approach, we could get these mice to be leaner on a high fat diet simply by administration of the chemical. This suggests that acute inhibition of the ALK7 receptor can prevent obesity in adult animals, says Tingqing Guo, first author of the study.

We have also showed that the ALK7 receptor works in a similar way in human fat cells as it does in mice.

Overall, these results suggest that blockade of the ALK7 receptor could represent a novel strategy to combat human obesity, says Carlos Ibanez, principal investigator of the study.

The work was supported by grants from the European Research Council, Swedish Research Council, Strategic Research Program in Diabetes of Karolinska Institutet, Swedish Cancer Society, Knut and Alice Wallenberg Foundation, the National University of Singapore and the National Medical Research Council of Singapore. eLife is a peer-reviewed open-access scientific journal established at the end of 2012 by Nobel Prize Winner Randy Schekman, with support from the Howard Hughes Medical Institute, Max Planck Society and Wellcome Trust.

The paper is freely accessible and can be found HERE.

New Call: Postdoc Fellows in Neurobiology | Metabolism

Work at Carlos Ibanez laboratory focuses on understanding the functions and signaling mechanisms of  growth factors and their receptors in neural development and injury responses and metabolic regulation, for the development of better therapies to diseases of the nervous system and metabolic disorders.

Carlos Ibanez is Professor of Neuroscience at the Karolinska Institute in Stockholm, Sweden.

Postdoctoral fellows are currently being recruited to the laboratory to advance research on growth factor receptor signaling and function in neurodevelopment and neural injury. We are seeking talented, innovative and enthusiastic researchers with a PhD awarded within the last 5 years. Candidates with expertise in i) molecular and cellular neurobiology, neurodevelopment or ii) molecular and cellular endocrinology, metabolic research and iii) 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 2014.

Deadline for application is May 10, 2014