Exjobbsförslag från företag

Detta är ett uppsatsförslag hämtat från Nationella Exjobb-poolen. Klicka här för att komma tillbaka till samtliga exjobbsförslag.

Förslaget inkom 2007-09-20

Molecular pathways in control of melanoma cell growth, invasion and apoptosis

The incidence of melanoma is rising and so far only surgical treatment can be used with efficiency on benign non-invasive melanoma. At this point there is no effective treatment for invasive melanoma since this cancer is resistant to available chemotherapy and radiation. The transformation from benign to malignant melanoma is accompanying by several molecular changes. Out of which the induction of the integrin avb3 is considered one of the significant causative changes. Our data show that melanoma cells with the expression of integrin avb3 have an inactivated tumor suppressor p53 protein (Bao et al., 2004 ). This inactivation may be the cause of melanoma resistance to therapy.

The overall aim of our studies is to find target molecules for treatment of melanoma. We attack this aim from several angles.
• We screen small organic compounds to activate p53 and kill melanoma cells.
• We characterize the molecular pathways between the attachment receptor integrin avb3 and the tumor supressor p53.
• We characterize the molecular pathways between the integrin avb3, activation of the oncogenes B-raf or N-ras for regulation of melanoma cell survival.

Experimental model
We use melanoma cells with or without the expression of integrin avb3 and culture them in collagen-gels. This model system is also called 3 dimensional cell culture and is used to mimic the 3D environment in the skin.

Possible ex-jobbs
*Melanoma cell lines with different expression of Integrin avb3 should be cultured in 3D collagen and investigated in terms of apoptosis, B-raf kinase activity and p53 status. Methods. Cell culture, in vitro kinase assay, flowcytometry, Western Blot.
*Set up 2D gel-electrophoresis to analyse p53 conformation and post-translational modifications. Methods. 2D gel-electrohporesis, Western blot, immunoprecipitation and cell culture.
*Different genes coding for proteins involved in Integrin avb3 signalling should be cloned into lentivirus-vectors. Methods. Molecular subcloning, gene-transfer, Western Blot, flowcytometry.

Minna Thullberg, Xu Zhao and Staffan Strömblad, Department of Biosciences and Nutrition at NOVUM,Huddinge, Karolinska Institutet.
Forskargruppen leds av Staffan Strömblad är ca 12 personer stor. 3 personer arbetar i melanomprojektet med nära samarbete med Galina Selivanovas grupp på MTC, KI, Solna.

Bao et al., Journal of Cell Biology, 2004


Informationen om uppsatsförslag är hämtad från Nationella Exjobb-poolen.