PhD stipend in the project OPUS NCN entitled: “Study of transcriptional networks disruption on the development of liver cancer”

20.06.18

Position:

PhD stipend in the project OPUS NCN entitled: “Study of transcriptional networks disruption on the development of liver cancer”

Project description:

The HNF4A gene is one of an array of genes involved in organogenesis and in modulation of the cancer development process in liver. In particular, it is known in mice, which removal of this gene from the genome, leads to tumour development in liver. Hence, it is postulated that any loss-of-function variation to the gene structure/composition (mutation) can trigger liver cancer development and its progression. As far, a throughout functional analysis of the HNF4A mutations in human liver cancer have not been performed. This study will allow us to investigate for the first time the importance of the HNF4 gene mutations in liver cancer. We have already found that the HNF4 mutations are accumulated at the evolutionally sustained regions of the gene, which is partly the reason of our interest in those mutations. Since the HNF4A gene modulates liver tissue differentiation and liver cancer cell fate, the loss of its function is associated with a poor prognosis. Our study aims to demonstrate that pathogenic mutations of HNF4A cause dysregulation of several gene expressions and induce hepatic tumorigenesis. Therefore, the immediate gain in knowledge expected from this project is evaluation of the role of the HNF4A mutations in liver cancer onset. However, given the increasing information on single DNA units’ variants and alterations of their copy number stemming from the many cancer sequencing projects going on world-wide, there is strong need of functional validation to identify potential drivers – a pre-requisite to translate this knowledge into new diagnostic or therapeutic leads. For this reason, we perform functional study of HNF4A mutations as a model case. Our preliminary results show that the mutations of the HNF4A gene result in impaired gene functionality. We have also identified three mutations located within another region of the gene which all resulted in a reduction of the gene activity. Although we found that HNF4A mutations are possible pathogenic mutations, it is unclear how the HNF4A mutations impact the pathogenesis of liver cancer. To answer this question, we will introduce mutations using CRISPR-Cas9 system in mouse and human normal liver cell lines and subsequently perform functional assays. Gene mutations can lead to altered gene function and malignant cellular transformation. To improve the early detection of mutations, it is indispensable to have a complete map of cancer driver genes and their hot spots. Our study aims to support the ongoing efforts at improving the early detection of cancers, thereby contributing to the field of preventive medicine. Although the modern molecular tools have let us determine multiple mutations linked to several cancers, the data comes only from limited number of countries. Our study may help to identify pathogenic mutations without performing tedious analyses, but by using an already existing dataset.

Description of the tasks:

Task 1: To test whether Zn finger mutations of HNF4A cause dysregulation of transcriptional networks and induce hepatic tumorigenesis.

Task 2: To investigate whether HNF4A ligand domain mutations cause liver cancer development through disrupting their binding specificity to target promoters and their co-factors, which changes the alterations in its transcriptional networks.

TYPE of NCN grant:

OPUS – NZ5

Deadline for application:

30.07.2018, 16:00

Form of application:

e-mail (h.taniguchi@ighz.pl)

Employment conditions:

• Selected candidate will receive a stipend of 3 000 PLN per month
• Place of employment:

Institute of Genetics and Animal Breeding of the Polish Academy of Sciences

• Employment starting date: October 2018
• Length of employment (scholarship): 28 months

Qualifications:

1. Master in veterinary, biotechnology, biology or related discipline;
2. Knowledge in the field of veterinary science, molecular and cellular biology;
3. Knowledge in the field of gene editing and in vitro cultures;
4. Ability to use the following techniques: Western blot, PCR and immunofluorescence staining of proteins in the cell;
5. Experience or knowledge with CRISPR-technique is advantageous;
6. Ability to communicate fluently in English;
7. Ability to communicate well and work in a group;
8. Ability to work under the time pressure

Additional information:

Scholarship will be granted according to the rules described in documents “Regulations on awarding scholarships in NCN-funded research project”.

Interested candidates are asked to provide the following documents:

1. Motivation letter;
2. CV including list of publications, conference presentations, membership in scientific organizations and other awards;
3. Master degree certificate
4. Recommendation letter from a scientific mentor, confirming skills necessary for completing the project;
5. Documents confirming proficiency in foreign languages;
6. Other documents, that in the opinion of the candidate are important when considering him/her for the position;
7. Signed statement: I hereby authorize you to process my personal data included in my job application for the needs of the recruitment process in accordance with the Personal Data Protection Act dated 29.08.1997 (uniform text: Journal of Laws of the Republic of Poland 2002 No 101, item 926 with further amendments).

Applications in English should be sent to: dr. Hiroaki Taniguchi
(h.taniguchi@ighz.pl)

Please direct any questions referring to the project directly to the PI of this project:

Dr. Hiroaki Taniguchi

Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Department of Experimental Embryology
ul. Postępu 36a, 05-552 Jastrzębiec n/Warsaw, mazowieckie, Poland
e-mail: h.taniguchi@ighz.pl

INFORMATION OBLIGATION

1. The administrator of personal data collected during the recruitment process is the Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, entered into the register of institutes of the Polish Academy of Sciences (kept by the Polish Academy of Sciences) under the number RIN-V-32/98, NIP no. 1230018381, REGON no. 000326196, address: Jastrzębiec, ul. Postępu 36A, 05-552 Magdalenka.
2. Personal data provided to the Administrator by the participants of the recruitment process will be processed in accordance with the provisions of the Regulation of the European Parliament and of the Council (EU) 2016/679 of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation) (OJ.EU.L. of 2016 No. 119/1, hereinafter referred to as "GDPR").
3. According to art. 5, 6, 7 and 13 of GDPR, the Administrator informs that:
   1. Personal data provided by the participant of the recruitment process will be processed on the basis of art. 6 par. 1 letter a) of GDPR, i.e. on the basis of their consent and in the range  which is necessary to appropriate realization of PhD studies in English

1. The person involved in the recruitment process has the right to request access to personal data, correct or remove it, as well as limit its processing, oppose to data processing, the right to transfer data and the right to submit a complaint to the supervisory body.
2. The person participating in the recruitment process has the right to withdraw consent to the processing of data at any time, which does not affect the legality of the processing which had been carried out on the basis of consent granted before its withdrawal.
3. Providing personal data by a person participating in the recruitment process is voluntary, however, the failure to provide it may prevent this process from being carried out.

       4. In all matters related to the processing of personal data of persons participating in the recruitment process, please contact the Institute in writing at the following address: daneosobowe@ighz.pl

After Decision of Scholarship Commission Mrs Effi Haque and Mr Aamir Teeli have received PhD stipends.