Giessen International PhD Programme 2008 Germany: Deadline This Week

July 15, 2008

Giessen International PhD Programme 2008

Deadline 17th July 2008.

We are searching for highly motivated and intelligent PhD-Students with good technical skills and with an experimental background in Reproductive Medicine, Morphology, Cell Biology or Molecular Biology. Specifically, such candidates should address “the role of peroxisomes in the testis and for male fertility”. For exact project description see below. Candidates should have a degree (Diploma or Master) in a field of Biomedical Science (such as Medicine, Veterinary Medicine, Human Biology, Biology, Pharmacy or related sciences).

Candidates will be integrated within the environment of the “Giessen Graduate School of Life Sciences” into an ambitious and international group with friendly and open-minded people (Medical Cell Biology -Director: Prof. Baumgart-Vogt). Our homepage:
http://www.med.uni-giessen.de/anat/ebv_new_hp/entrance.htm .

See project within “The Giessen Graduate School of Life Science”:
http://www.uni-giessen.de/cms/fbz/zentren/ggl/application/open-projects .

GGL Section 6 “Reproduction in Man and Animal”
Project from Prof. Baumgart-Vogt:

The deadline for the application for the GGL and the PhD programme 2008 has been extended to Thursday 17th July 2008 (this week!)for the projects in Reproductive Medicine of the Clinical Research Unit (KFO 181/Project, funded by the German Research Foundation). The decision will be definitively made this Friday 18th June. Therefore, please send your applicaton latest on Thursday until 2 pm (14:00).
In case we are interested, we will call you back immediately on Friday, therefore make sure to leave a telephone number under which we can reach you directly.
Start of the Project will be 01.09.2008 or 01.10.08 depending on the availability of the students.
For German students: payment according to BAT IIa/2.
For international students: scholarship of 1.000 €/month.

Project description:

Role of peroxisomes in the testis: Analysis of testicular dysfunction in peroxisomal diseases and of peroxisomal functions in idiopathic male infertility.

Aims/Hypotheses:
1. To characterize the peroxisomal metabolism in distinct cell types of the testis (Leydig-/ Sertoli-/germ cells) and its influence on the physiological regulation of spermatogenesis
2. To analyze the pathological consequences of peroxisomal dysfunction in the testis
3. To identify peroxisomal candidate genes altered in patients suffering from infertility.

Review of present state of knowledge and preparatory work:
Peroxisomes are ubiquitous cell organelles with main functions in the metabolism of reactive oxygen species (ROS) and lipids (Wanders 2004). They exhibit very heterogeneous enzyme composition in distinct organs and cell types (Baumgart 1997). In testis peroxisomes have been localized morphologically mainly in Leydig cells (Reddy and Svoboda 1972, Reisse et al 2001). However, recent work from our groups has revealed that these organelles are also present in addition in Sertoli and germ cells, exhibiting a heterogeneous enzyme composition for marker proteins (Nenicu et al 2007).
Even though nothing is known on the functional relevance of peroxisomal metabolic pathways in the distinct cell types of the testis, the vital importance of peroxisomal metabolism for male fertility is stressed in patients with peroxisomal diseases. Male patients with peroxisomal disorders exhibit dysfunction of spermatogenesis up to infertility (for reviews see: Powers 1985, Dimmick 1997). Similarly, male knockout mice with deficiencies in peroxisomal lipid metabolism are infertile (Fan et al 1996, Rodemer et al 2003, Huyghe et al 2006). In addition, Sertoli cell-specific PEX5-KO mice deficient in peroxisome biogenesis develop spermatogenic arrest up to complete testicular atrophy (Huyghe et al 2006).

Workplan:
The effects of peroxisome dysfunction on male fertility will be analyzed in situ and in primary cell lines of testicular cell type-specific “peroxisomal” kockout mice. PEX13flox mice (Bjorkman et al 2002) already present in our laboratory will be crossed with Sertoli- and Leydig cell-specific cre-mice to knockout peroxisome biogenesis and to induce the deficiency of all peroxisomal metabolic pathways in these cell types. These mice will be analyzed in comparison to control animals for dysregulation of spermatogenesis and for testicular pathologies with the techniques already established by our group for other, generalized peroxisomal knockout mice (Baes et al 1997, Baumgart et al 2001, Li et al 2002 a,b). The relevance of peroxisomal metabolism for the alteration of distinct testis-specific regulatory pathways (e.g. FSH-, LH-, acitivin/inhibin-, TGFb- as well as RXR-, LXR-, PPAR-signalling or steroid synthesizing pathways) will be revealed by cell type-specific microarray an!
alysis with Code-link oligonucleotide arrays in collaboration with Project 6 der KFO. Subsequently, interesting results of selected gene alterations will be verified by quantitative RT-PCR on Sertoli- and Leydig cell-specific RNA of control or cell-type-specific PEX13-KO mice with peroxisome deficiency. Alterations of steroids and fatty acids in the testis of cell-type specific PEX13 KO- versus control mice will be analysed by GC-mass spectrometry in cooperation with Prof. Wudy (Department of Pediatrics, JLU Gießen) and Dr. Okun (Department of Pediatrics, University of Heidelberg). Functional analyses will be done in primary cell cultures (e.g. ROS-measurements in distinct cell lines in the presence or absence of antioxidants; effects of lipids, testosterone/oestrogen, cytokines or growth factors on cell cultures).
Human testis biopsies with mixed atrophies will be screened to identify peroxisomal candidate genes possibly involved in the development of idiopathic testicular infertility in man. Analysis will be done on Paraffin or frozen sections with the above mentioned methods in conjunction with laser microdissection to compare seminiferous tubules with distinct pathologies and to isolate cell-type specific RNA for hybridization with our “all known peroxisomal genes” cDNA microarray.
The data of this study will help to clarify the functional role of peroxisomes of distinct cell types in the testis for male fertility and to find possible peroxisomal candidate genes involved in the development of idiopathic infertility in man.

For further information, please feel free to send an E-Mail to:
Eveline.Baumgart-Vogt@anatomie.med.uni-giessen.de .

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