Understanding drug resistance by characterization of transcription factor complexes by mass spectrometry

Background
Mass spectrometry based proteomics has advanced rapidly the last years with improved sensitivity and robust protein identifications and quantifications. Our group use mass spectrometry based proteomics methods to understand and predict breast cancer treatment. Breast cancer is the most common form of cancer among women and one of nine women will develop breast cancer during their lifetime. Estrogen exposure is an important risk factor for developing breast cancer, contributing to the growth of 80% of the tumors that are estrogen receptor positive. Consequently, adjuvant endocrine therapy with the antiestrogen tamoxifen, the first targeted cancer therapy, has been the cornerstone for estrogen receptor positive breast cancer for 3 decades. Endocrine resistance is a serious clinical problem as one-third of the patients relapse. Hence, basic understanding of estrogen biology and resistance mechanisms is needed to define drug targets and combinations thereof, as well as new markers to guide patient treatment
Tumors become resistant to treatment of drugs by altering intracellular signaling, protein levels and protein complex composition. The aim is to increase understanding of these mechanisms by characterizing protein complexes in response to natural ligands and drugs in drug responsive and resistant cell lines.

The group
The research group is composed of 18 people with different background as molecular biology, biochemistry, medical doctor, bioinformatics and statistics. Of these, 4 persons focus on breast cancer.

Work description
The work will include basic molecular biology and biochemistry methods as cell culturing, subcellular fractionation, and methods to pull down protein complexes. The samples will be characterized by nanoLC-MS/MS and validated by western blot, siRNA and proximity ligation. Interesting findings will be validated in patient samples.

Qualifications
Cell culture experience is preferable but not necessary. Basic understanding and a genuine interest of cellular biology and function is necessary.
Some previous understanding in mass spectrometry is positive but not any requirement. A general interest in proteomics is needed.
You are drifted, get things done and are self going.

Application procedure
Send by E-mail:
- CV
- Finished course with grades (if not listed in CV)
- A letter explaining briefly your interests and motivation

Start in the spring of 2012 or after agreement!
30-60 hp

Contact 1 (primarily)
Henrik Johansson | PhD
Clinical Proteomics| Mass Spectrometry
Dept. Oncology-Pathology | Karolinska Institutet
Science for Life Laboratory | Alfa floor 1| Tomtebodavägen 23A
Box 1031 | SE-171 21 Solna | Sweden
Phone +46 8 524 81210 | Cell +46 769 471179
E-mail: [email protected]
scilifelab.se | ki.se/onkpat


Contact 2
Janne Lehtiö | PhD
Associate Professor | Proteomics|
Clinical Proteomics Mass Spectrometry | Karolinska Institutet | SciLifeLab Stockholm
Science for Life Laboratory | Box 1031 | SE-171 21 Solna | Sweden
[email protected] | [email protected] | scilifelab.se | +46 8 524 81416 |http://ki.se/ki/jsp/polopoly.jsp?d=32617&a=103389&f=sv&l=en |