Working Group 4

Functional Genomics and Therapy

This WG will functionally validate candidate genetic variants from germline or tumor studies by using cutting-edge approaches such as CRISPR- Cas9 gene editing. On the other hand, it will generate novel approaches such as organoids / zebrafish avatars to implement (chemo)therapeutic strategies based on the patient in an effort to implement personalized medicine for PDAC.  

Objectives

  • To link unequivocally genetic variants with an altered gene function or pathogenicity.

  • To establish organoids / zebrafish avatars using xenografts from PDAC patients.

  • To select the germline and somatic candidate genetic variants to be functionally investigated.  
  • To perform gene editing for the selected genetic variants by using CRISPR-Cas9 and reintroducing them in cell cultures.  
  • To study the alteration of cellular processes and the specific gene function in the transfected cells, comparing the studied genetic variant and their wild-type counterpart. 
  • To assign pathogenicity to genetic variants if an alteration is detected in previous studies. 
  • To use organoid / zebrafish xenograft models mimicking the in vivo PDAC tissue to better characterize patients’ response to therapy.  

Tasks

Activities

Dedicated WG meetings will take place (1-2 per year). Workshops on the field will be included during meetings. A training school will be committed to the topic of gene editing. Inter-laboratory exchanges in the form of STSMs are also envisioned especially for young researchers. A tight monitoring of the WG activities will be ensured by a strong WG committee.  

  • Establish a zebrafish avatar for PDAC patients.

  • Combine multi-omics with organoid / zebrafish avatar data to obtain a patient profile.

  • Establish a model of gene editing for potentially druggable mutations.

  • Establish an exchange of organoid models.

Milestones

Objectives

  • To link unequivocally genetic variants with an altered gene function or pathogenicity.

  • To establish organoids / zebrafish avatars using xenografts from PDAC patients.

Tasks

  • To select the germline and somatic candidate genetic variants to be functionally investigated.  
  • To perform gene editing for the selected genetic variants by using CRISPR-Cas9 and reintroducing them in cell cultures.  
  • To study the alteration of cellular processes and the specific gene function in the transfected cells, comparing the studied genetic variant and their wild-type counterpart. 
  • To assign pathogenicity to genetic variants if an alteration is detected in previous studies. 
  • To use organoid / zebrafish xenograft models mimicking the in vivo PDAC tissue to better characterize patients’ response to therapy.  

Activities

Dedicated WG meetings will take place (1-2 per year). Workshops on the field will be included during meetings. A training school will be committed to the topic of gene editing. Inter-laboratory exchanges in the form of STSMs are also envisioned especially for young researchers. A tight monitoring of the WG activities will be ensured by a strong WG committee.  

Milestones

  • Establish a zebrafish avatar for PDAC patients.

  • Combine multi-omics with organoid / zebrafish avatar data to obtain a patient profile.

  • Establish a model of gene editing for potentially druggable mutations.

  • Establish an exchange of organoid models.