Doktorander/Utbildningsplatser

Doktorander/Utbildningsplatser
med placering vid Sahlgrenska akademin

Sista ansökningsdag: 2010-04-20

Sahlgrenska akademin utlyser doktorandplatser med placering vid institutionen för biomedicin, institutionen för kliniska vetenskaper, institutionen för medicin och institutionen för neurovetenskap och fysiologi.

Doktorandplatserna avser två års utbildningsbidrag och två års doktorandanställning, alternativt fyra års doktorandanställning, och beräknas leda fram till doktorsexamen.

För mer information och ansökningsblankett se:
http://www.sahlgrenska.gu.se/doktorandportalen/Doktor_Fran_start_till_mal/doktorandplatser


The ubiquitin-proteasome system and oxidative stress/antioxidative mechanisms in the eye lens - implications for cataract formation

Application deadline: 2010-04-20

Description of the research project
Cataract (swe: grå starr) is defined as an opacification of the eye lens leading to impaired vision.Although being the most common cause of blindness worldwide, the exact mechanism behind cataract formation is not known.Epidemiologic, as well as experimental studies, have implied oxidative stress as an important pathogenic factor in cataractogenesis.Oxidative changes to lens proteins are known to cause aggregation of these modified proteins, leading to light-scattering lens opacities.In this context, proteolytic removal of defect proteins is important to prevent opacification of the lens.In mammalian cells, the ubiquitin-proteasome system is responsible for enzymatic degradation of oxidized or otherwise aged proteins.
The present PhD-project will investigate interactions between the ubiquitin-proteasome pathway and oxidative stress/antioxidative mechanisms in the lens.Following oxidative challenge induced by UVB-radiation, changes in the amount of oxidized lens proteins and the proportion of proteins labelled with ubiquitin for subsequent degradation by the proteasome will be monitored, as well as changes in enzymatic activity of the proteasome.Oxidation of lens proteins and effects on proteasome activity will also be investigated in lens epithelial cells generated from superoxide dismutase (SOD) knock-out mice.A new cataract model, using anti-sense technique to down-regulate the SOD gene in zebrafish, will also be established and evaluated.In addition, the PhD-project comprises two case-control association studies on polymorphisms in the SOD gene and in the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene respectively, the latter gene product being involved in ubiquitin-deconjugation of proteasome substrates.

Hence, the PhD-project described above aims to investigate two putative pathogenic mechanisms behind cataract formation; proteolysis and oxidative stress, using various techniques ranging from molecular biology and enzyme kinetics to genetic analyses on clinical material.
Desired background
Theoretic knowledge and hands-on experience of techniques to be used in the described project is desired, i.e.cell culture, morphologic techniques, proteolytic assays, molecular biology and gene analysis.