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Project descriptions JCF call January/February 2014

You will find three (3) projects here.

View application as pdf.

Project 1

Project leader:

Matthias Hentze, Martina Muckenthaler

Project supervisor:

Matthias Hentze, Martina Muckenthaler

Affiliation:

Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany. Webpage

European Molecular Biology Laboratory Heidelberg (EMBL), Heidelberg, Germany. Webpage

Start of MD project:

asap

Project description

Title:

Molecular characterization of the iron exporter ferroportin

Summary:

Iron homeostasis is maintained by the iron hormon hepcidin, which binds to the iron exporter ferroportin. Ferroportin is essential for dietary iron uptake in duodenal enterocytes and for the release of iron from macrophages that recycle damaged red blood cells. Impairment of the hepcidin/ferroportin regulatory system causes frequent disorders of iron metabolism, including iron overload and iron deficiency diseases. The project will focus on the molecular analysis of ferroportin. Based on structural information defined ferroportin mutations will be analyzed to assess their role in the activity of the protein.

References:

Altamura et al. Hepcidin binding to ferroportin prevents exocrine pancreatic insufficiency and fatal iron overload. Cell metabolism (in press).

Hentze MW, Muckenthaler MU, Galy B, Camaschella C: Two to tango: regulation of Mammalian iron metabolism. Cell 2010, 142(1):24-38.

MMPU Website:

Research Group Iron Homeostasis

Contact:

Martina.muckenthaler@med.uni-heidelberg.de

hentze@embl.de

Project 2

Project supervisor:

Jan Siemens

Affiliation:

Department of Pharmacology, Heidelberg University  Webpage

Start of MD project:

Flexible; Preferred: Beginning of 2015

Project description: 

Title:

The Role Of Mast Cells In Inflammatory And Neuropathic Pain

Summary:

Pain serves an important function to facilitate protective reflexes in order to prevent tissue damage and to promote healing. However, persistent (chronic) forms of debilitating pain are a huge burden to patients and society. Immunological responses and inflammatory mediators play an important role in modulating pain signals that are generated by peripheral sensory neurons. A large variety of different inflammatory mediators (the so called inflammatory soup) sensitize nociceptive neurons resulting in decreased pain thresholds. However, the source of the inflammatory mediators and their relative contribution to pain sensitization in the context of pathological pain states are largely unknown. Among the different immune cells, Mast cells appear to be prime candidates to modulate pain signals as they are frequently found in close proximity to nociceptive neurons. Additionally, Mast cells are a reservoir of a variety of different inflammatory mediators. A number of studies have implicated Mast cells in the pathology of persistent forms of pain. However, the lack of a specific Mast cell model limits the conclusions that can be drawn from these studies. Here, using a mouse line specifically depleted of Mast cells, this project aims to elucidate the role Mast cells in models of inflammatory and neuropathic pain.

References:

Mast cells: Versatile gatekeepers of pain, Mol Immunol. 2014, S0161-5890(14)00054-6

Cre-Mediated Cell Ablation Contests Mast Cell Contribution in Models of Antibody and T Cell-Mediated Autoimmunity, Immunity 2011, 35, 832–844

MMPU Website:

Research Group Chronic Pain

Methods:

Behavior experiments  (nocifensive response measurements) using Mast cell deficient mice

Cooperation partners:

Hans-Reimer Rodewald, DKFZ

Personal Qualifications:

We are looking for an enthusiastic candidate with an interest in sensory neuroscience at the interface with Immunology. Previous experience in the handling of laboratory animals (rodents) would be an asset.

Keywords:

Mast cells; Pain; Sensory Neurons, Cytokines; Neuro-Immune Interactions

Contact:

Ulrike Baur-Finck

Project 3

Project leader:

John Briggs

Project supervisor:

John Briggs/ Hans-Georg Kräusslich

Affiliation:

EMBL Webpage

Start of MD project:

as soon as possible

Project description: 

Title:

Application of cryo-EM to resolve structures of medically important integral membrane proteins.

Summary:

Many medically relevant proteins are integral membrane proteins; including drug and ion transporters, signal receptors and viral glycoproteins. Structural information on these proteins is valuable in understanding their mechanisms and in developing compounds that modulate their function. Integral membrane proteins are, however, challenging to study by structural biology methods. Recent breakthroughs in cryo-electron microscopy have made it possible to determine the structures of integral membrane proteins without crystallization. In this project the MD student will develop and optimize protocols for the preparation of membrane proteins for cryo-electron microscopy, and will then apply cryo-electron microscopy and image processing methods to determine their structures. They will then interpret these structures to derive an understanding of the mechanisms by which the proteins carry out their biological function.

MMPU Website:

Research group HIV 1 formation and its inhibition

Methods:

Cryo-electron microscopy, protein biochemistry

Contact:

briggs@embl.de