Additional recruitment to the Doctoral School of Natural Sciences  beyond the limit of places 

Project description 

Our bodies comprise of approximately 200 cell-types each carrying the same genome but executing only part of the genetic information specific to their type. Cell-type specific identity is established during development through cell differentiation driven by numerous inter- and intra-cellular mechanisms and secured with epigenetic cellular memory. Securing expression of cell-type specific  gene sets requires efficient control and precise fine-tuning which is achieved through many different molecular pathways.  

Each of the genes needs to be specifically recognized by the transcription machinery from the pool of more than 60 thousand of human transcription units buried within 2 meters of DNA. It needs to be activated: 1) at appropriate level, 2) when needed and 3) for distinct time. Reading of the genomic information needs not only start but also finish at distinct place so as not to activate information from neighboring gene.  

Transcriptional complexity and specificity are further extended by the fact that most of the genes have alternative beginnings and endings. We have previously described a mechanism of gene control by transcription termination for a subset of genes in mammalian cells.  We have found that for efficient gene expression it is important to finish reading of genetic information in the right place and discovered that activity of some genes is regulated by premature finishing.  

Our recent analysis of transcription termination with mNETseq methodology which specifically identifies termination events with unprecedented precision showed that many sites of both premature and full-length (normal) termination are enriched with architectural proteins CTCF, MAZ as well as cohesins which are important for 3D organization of the genome in the cellular nucleus. Analysis of 3D genome folding revealed that those sites are frequently associated with genomic loops which in many cases are anchored within the termination sites -premature or normal. In yeast it has been previously found that multiple factors binding to DNA can form a roadblock, which facilitates RNA polymerase II termination. I hypothesize that the chromatin loops we observe at mammalian terminators are a roadblock that might facilitate transcription termination. In the proposed research I would like to investigate whether observed genomic loops can help with premature finish of reading of the genomic information. If this is true, then loops at termination sites would be an important element of gene activity regulation.  

To test our hypothesis at the single genomic site level we will remove genomic loops on chosen 2-3 premature termination sites. We will achieve this by deleting their anchoring sites without affecting of the termination signal using CRISPR-Cas9 genome editing methodology. Than we will analyze whether transcription was affected. Later for genome-wide overview we will remove all the loops by fast removal of the cohesin – molecular complex involved in loop formation, using degron methodology. This will be also followed with analysis of nascent transcription. Those two sets of orthogonal and complementary experiments will independently show what is the importance of chromatin loops on premature termination at both global and local scales.   

The proposed research will elucidate the role of chromatin loops at premature and normal termination sites. It will extend our understanding of gene expression regulation. In the long term, such novel aspect of transcription control may be important for understanding of pathogenesis of diseased caused by mis-regulated genes and could contribute to development of new lines of treatment.

Principal investigator: dr hab. Michał Gdula  projekt NCN Preludium BIS 2023/50/O/NZ2/00660

Recruitment:

Selection Committeee       

Recruitment fee

The recruitment fee is 75 EUR.

Form of the selection procedure

Two-stage procedure.

Language of the selection procedure, including interviews:

Polish or English language. 

Required documents:

 1.        Candidates who have obtained the necessary education outside the territory of the Republic of Poland, shall additionally submit:

1)    a photocopy of a document which confirms their education, certified to be a true copy of the original document, i.e. a diploma with a supplement confirming completion of first cycle studies (Bachelor degree) and a diploma with a supplement confirming completion of second cycle studies (Master degree, MSc, MA) in the original language and in a certified translation into English or into Polish,

            2)    a photocopy of their passport. 

 Evaluation criteria

 1)    the grade awarded for the diploma of the second cycle studies or single cycle five year master’s studies - maximum 10 points; in the case of candidates who seek admission on the basis of superior academic achievements ("Pearls of Science") - 10 points;

 2)    evaluation of the candidate's scientific activity and scientific achievements; the candidate indicates for evaluation up to three documented scientific achievements, in accordance with the achievement criteria adopted by the selection committee for a given discipline - maximum 15 points;

 3)    evaluation of the candidate's other documented activity, based on a maximum of three achievements consistent with the achievement criteria adopted by the selection committee for a given discipline - maximum 5 points

 4)    the result of the interview, with the scope of the interview including:

 a)    the candidate's knowledge and competencies relevant to the planned research and appropriate to the indicated scientific discipline,

 b)    elements of research methodology appropriate for the discipline indicated.

 No more than 50 points can be awarded for the interview; the maximum duration of the interview is 30 minutes.

 5)    evaluation of the research project prepared and submitted for assessment to the selection committee (maximum 20 points), with particular emphasis on:

 a)    the ability to formulate the research objective and present the research problem;

 b)    research idea and the ability to propose a solution;

 c)    methodology appropriate to the discipline indicated;

          d)    knowledge of the state of research with a basic bibliography. 

Condition of admission to the Doctoral School 

Education Program

Education at the doctoral school lasts 8 semesters. Education at the Doctoral School  is offered on the basis of a framework curriculum and an individual research plan and ends with the submission of a doctoral dissertation.

The framework curriculum at the doctoral school includes a catalogue of modules of compulsory classes, elective compulsory classes and optional classes. It also:

1)    defines their schedule

2)    defines the way in which the classes are taught

3)    defines how learning outcomes are verified.

Supervisors

A doctoral student works under the supervision of a supervisor or supervisors, or a supervisor and auxiliary supervisor, who will be appointed by the Deputy Rector at the request of a doctoral student (within 3 months of the start of his or her studies at the Doctoral School).

Scholarships 

The scholarship is PLN 5,000 (gross-gross)  for the first two years and PLN 6000 (gross-gross) for the next two years.