Nebal Badra - ESR 4
Name: Nebal Badra
Main Host Institution: Department of General Biology, School of Medicine, University of Patras (Greece)
Academic Background: I studied for a BSc in Biology from the University of Granada (Spain) in 2014 where I acquired expertise in Biochemistry of Human Pathology.
In 2015 I studied towards an MSc in Regenerative Biomedicine at Biomedical Research Center (CIBM) where I found my passion about researching. One year after that, in 2016, I also studied for a MSc in Biological Analysis and Laboratory Diagnosis at the Department of Pharmacy of the University of Granada where I kept improving my research skills. I am currently conducting my PhD at the Cell Cycle Laboratory in the Medical School of the University of Patras, where we study cell cycle control and maintenance of genome integrity.
Project title: Identification of synthetic lethal interactions with DNA replication licensing aberrations.
Project background: During cell division, proliferating cells must be precisely regulated to ensure that the information contained in their genome is duplicated just once per cycle. A disruption in the mechanism controlling DNA replication can lead to genome instability, a hallmark of tumorigenesis. Cdt1 has a pivotal role in cell cycle regulation by loading the MCM2-7 complex to the chromatin-bound origin recognition complex, promoting the formation of the pre-replicative complex (pre-RC) and therefore contributing to origin license. A deregulation in Cdt1 or its inhibitor Geminin was shown to be related to re-replication in higher eukaryotes through the reassembly of the pre-RC, which in turns induces the activation of checkpoint and DNA repair pathways to prevent and overcome DNA damage to the cell. Thus, loss of replication licensing regulation requires some of these pathways intact to prevent replication stress and genomic instability. Importantly, Cdt1 and Geminin expression have been shown to be deregulated in cancer and they have been suggested as markers for cancer prognosis.
Synthetic lethality is defined as a combination of two mutations which together result in cell death. In anti-cancer therapy, synthetic lethality approaches rely on the knowledge of inherent differences between cancer and normal cells and exploit the malignant-cell signalling complexity, providing an opportunity to specifically target cancer cells. Our rationale is to identify target genes required for cancer-cell survival when coupled with a deregulation in replication licensing and to characterize chemical compounds which compromise DNA replication licensing.
- To identify synthetic lethal interactions between the DNA damage response and DNA repair pathways with a deregulated expression of the DNA replication licensing factor Cdt1 or its inhibitor Geminin.
- To characterize molecular targets for chemical compounds in DNA replication licensing.
Expected outcome: Pinpointing genes required for cancer cell surveillance coupled with DNA replication licensing deregulation. Characterize molecular targets of chemical compounds which impair DNA replication licensing.