7.4.2024
M.Sc. position available (now or latest October 2024) with the topic ‘Characterization of apoptosis inducing CDK-inhibitors in therapy resistant tumor cells with focus on anti- and pro-apoptotic proteins’ 

Scientific background
Apoptosis, or programmed cell death, plays a key role in the elimination of tumor cells. Apoptosis can be divided into two different signaling pathways that can trigger the endogenous suicide program. The so-called 'death receptor signaling pathway' is triggered after binding of natural ligands to death receptors such as TRAIL. The 'mitochondrial apoptosis pathway' is activated by DNA damage and cellular stress in the cell. Both signaling transduction pathways activate proteases of the caspase family, which lead to the death of the cell through proteolytic cleavage of vital cell proteins. 

Cyclin-dependent kinases (CDKs) play an important role in cell cycle regulation and transcriptional control, but can also influence apoptosis. CDKs can be separated in cell cycle CDKs (CDK4,6,1 and 2) and transcriptional CDKs (CDK7, 8, 9, 11, 12 and 13). Especially the inhibition of transcriptional CDKs induces apoptosis. The transcriptional CDKs regulate RNA-Polymerase II and therefore the transcription of a wide range of mRNAs. It is currently speculated that particularly the lack of transcription of the anti-apoptotic Bcl-2 protein Mcl-1 is the major mechanism for the apoptosis induction mediated by CDK-inhibitors. 

Due to the dual mechanism of pan-CDK inhibitors as proliferation- and transcription-inhibitors, these drugs are recognized as potential cancer therapeutics. Examples include SNS-032, Dinaciclib, which is already in clinical trials, and meriolins, which have been the focus of particular attention at our institute so far. 

Project description
The project includes the characterization of apoptosis initiation after treatment with different transcriptional CDK inhibitors. The expression levels of various proliferation proteins and anti-apoptotic proteins will be analyzed, and kinetics performed. Focus is placed on Western blot analysis. Other methods such as cell death and apoptosis assays (e.g. Alamar Blue assays, caspase-3 activity assays and flow cytometric Nicoletti assays) will also be performed. Within the project, there is close supervision by a PhD student as well as a weekly meeting with the head of the institute. 

Requirements
You should have some basic experience of laboratory and molecular biology work. It is an advantage if you have worked with cell biology systems and Western blots. In addition, you should have good English language skills. A high level of motivation and commitment to experimental work is required. 

Contact
Applications (including motivation letter, CV and certificates) should be sent to Prof. Sebastian Wesselborg (Sebastian.Wesselborg@uni-duesseldorf.de).

Es besteht die Möglichkeit, im Rahmen von naturwissenschaftlichen Studiengängen (z.B. Molekulare Biomedizin, Biologie, Medizin udgl.) eine Masterarbeit am Institut für Molekulare Medizin I anzufertigen. Es besteht zudem die Möglichkeit, eine medizinische Doktorarbeit am Institut für Molekulare Medizin I durchzuführen. Voraussetzung für medizinische Doktorarbeiten sind ein Freisemester plus die angrenzenden Semesterferien für die Durchführung der Experimente.

Bewerbungen für naturwiss. Masterarbeiten und med. Doktorarbeiten 
Anfragen für Masterarbeiten und med. Doktorarbeiten sollten folgende Kriterien erfüllen:

• Bewerbung ausschließlich per E-Mail mit kurzer Angabe (Masterarbeit oder Doktorarbeit und geplanter Zeitraum)
• die E-Mail muss als Anhang eine einzelne PDF-Datei enthalten mit:

1. Motivationsschreiben (max. 1 Seite)
2. tabellarischen Lebenslauf
3. Zeugnisse (Abitur, Bachelor, ggf. ein aktuelles 'Transcript of Records')

Anfragen bitte per E-mail an das Sekretariat des Instituts richten: MolekulareMedizin1@hhu.de