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Project title: Defining the role of p53 status on Keap1-mutant lung cancer sensitivity to glutaminase inhibition
The PhD education in Medical Science comprises carrying out a scientific project and completing at least 30 credits of courses at third-cycle level. The doctoral student must also write a scientific compilation thesis or monograph corresponding to at least 120 credits. For more information about third-cycle studies at Sahlgrenska Academy, see https://www.gu.se/en/sahlgrenska-akademin/doctoral-studies
Project: In order to support their growth, cancer cells need to increase their metabolic output, which results in higher oxidative stress. To compensate, tumor cells can either increase the import of exogenous antioxidants or upregulate the endogenous antioxidant response, which is coordinated by the transcription factor and antioxidant master regulator NRF2. Our lab is interested in studying the impact of the KEAP1-NRF2 pathway in cancer, with a major focus on lung cancer.
The PhD candidate will establish and validate murine and human lung cancer cells that are Kras-mutant but p53-wt. Through CRISPR/Cas9 mediated genome engineering, Keap1-mutant or Keap1-wt isogenic cell lines will be derived. Further on, p53 loss will also be induced in these cell lines to compare to p53-wt background. We will validate cellular growth and signaling properties of these cell lines and conduct metabolomic profiling in the form of labeled glucose and glutamine tracing experiments, as well as measuring antioxidant and ROS levels to elucidate the role of p53 status on Keap1-mutant LUAD sensitivity to glutaminase inhibition. Following in vitro characterization, we will also assay growth, metastatic potential, sensitivity to glutaminase inhibition in vivo, and whether there are any synergistic effects with standard of care chemo- and immune therapies in Keap1 mutant LUAD. Promising precision medicine targets will be followed up in pre-clinical trials in patient derived xenograft models, together with our clinical collaborators. This project should markedly increase our understanding of what subtypes of LUAD might respond to glutaminase inhibition and help identify better therapies for a significant portion of lung cancer patients.
The candidate should be interested in molecular and cell biology, and cancer. The work is highly collaborative, both within and outside the group. Therefore, good teamwork, communication, and presentation skills are important. The project requires a methodical, organized and enthusiastic person with a passion and curiosity for science. Excellent English is required.
Third-cycle studies are equivalent to four year full-time and lead to a Degree of Doctor. Those appointed to doctoral studentships shall primarily devote themselves to their studies. Those appointed to doctoral studentships may, however, work to a limited extent with educational tasks, research and administration (departmental duties). Before a PhD degree has been awarded, duties of this kind may not comprise more than 20 per cent of a full-time post.
To be eligible for third-cycle studies, the applicant must meet both the general and specific entry requirements.
A person meets the general entry requirements for third-cycle studies if he or she:
1. has been awarded a second-cycle qualification
2. has satisfied the requirements for courses comprising at least 240 credits of which at least 60 credits were awarded in the second-cycle, or
3. has acquired substantially equivalent knowledge in some other way in Sweden or abroad
A person meets the specific entry requirements for third-cycle studies in Medical Science if he or she has successfully completed the English B/6 course or is considered to have acquired equivalent knowledge through previous studies
In selecting between applicants who meet the general and specific entry requirements, their ability to benefit from third-cycle studies shall be taken into account. The assessment shall attach particular importance to documented qualifications for:
– specific knowledge and skills within the subject area and related research fields
– experience of scientific theory and relevant research methodology
– scientific analysis and presentation verified through thesis, degree project, scientific journals or the like.
Documented experience with different molecular and cell biology techniques such as human cancer cell culture, viral transduction, CRISPR/Cas9 gene editing, genetic engineering techniques, clonal expansion and clone picking, Western Blotting, gene expression analysis and in vivo work with mouse models of cancer is advantageous.
After admission to third-cycle studies you will be appointed to doctoral studentship. Regulations for employment of doctoral students are given in SFS 1993:100. The initial appointment may apply for no longer than one year. An appointment may be renewed for no more than two years at a time. A person may be appointed to a doctoral studentship for a total of eight years. The total employment period may, however, not exceed the time corresponding to full-time third-cycle study for four years.
Location: Sahlgrenska Academy, Institute of Clinical Sciences, Department of Surgery. Extent: 100%. First day of employment: as agreed.
Salaries for doctoral students are regulated in a local agreement at the University.
For further information regarding the position
For more information about the project please contact the principal supervisor,
Vokan Sayin, Institute of Clinical Sciences, e-mail: email@example.com
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How to apply
In order to apply for a position at the University of Gothenburg, you have to register an account in our online recruitment system. It is the responsibility of the applicant to ensure that the application is complete in accordance with the instructions in the job advertisement, and that it is submitted before the deadline.
You must include the following, in pdf format
- Personal letter
- Diploma and transcripts showing that you meet with the general entry requirement
- Proof of completion of English 6 course or the acquired equivalent knowledge through previous studies
If your degree is from a university outside of Sweden, make sure that you attach a diploma and full transcripts that makes assessing your degree easier.
If your degree has not been verified by a Swedish authority you need to provide contact details to the issuing university, registrar or similar, that can verify the degree at our request.
For information on what you need to submit in order to fulfill the English language requirement see https://www.universityadmissions.se/en/entry-requirements/english-language-requirements/
Closing date: 2021-06-22