Transcriptional analysis of chIFITM knockout technology for increased vaccine yields

Lead Research Organisation: University of Oxford
Department Name: Interdisciplinary Bioscience DTP

Abstract

"Avian viruses are a major consideration in poultry health management as they cause disease and significant economic losses. Vaccines are the main tool used to mediate this problem. Due to the growth of the poultry industry, manufacturers are under considerable pressure to lower the costs of vaccines and to produce them more efficiently. As vaccines are predominantly produced in cell culture or embryonated chicken eggs, the host immune response poses a significant bottleneck in production, thereby reducing viral yields. Previous research has shown that transient ablation of restriction factors, namely Interferon Inducible Transmembrane Proteins (IFITMs), enables the virus to establish a more successful infection and consequently raises the yield of virus particles.

In this project we propose to employ CRISPR/Cas9 gene editing technology to stably knockout individual chicken IFITM (chIFITM) genes, as well as the entire chIFITM locus. To evaluate the outcomes of these gene edits, RNA sequencing will be used to identify differentially regulated immune signalling pathways. This will provide crucial information on the downstream effects of gene editing and determine whether this is a sustainable approach for vaccine production optimisation."

AfS, ENWW

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011224/1 30/09/2015 29/09/2023
1985950 Studentship BB/M011224/1 01/01/2018 30/06/2022 Martina Hadrovic Sinthalapadi
 
Description We study the effect of loss of IFITM genes (IFITM KO)  on early immune response in influenza infection. Our model are two cell lines (DF-1 and PGC)  from different origin which offers an ability to estimate the importance and function of these genes depending how well the cells adapt to the loss and alter their response to the infection. Preliminary results of DF-1 KO show they become more susceptible to viral infection while PGC KO more resistant. These contrasting results are very intriguing and will offer us an opportunity to investigate how loss of same genes can alter different signalling networks and result in different outcomes.
Exploitation Route DF-1 cell line is a widely used tool in avian immunology research, especially in influenza investigations. Characterising DF-1 immune response in the level of detail as in this project will inform further studies on suitability of the model and considerations that must be taken into account when using it. These cells are also being considered for use by manufacturers in biotechnology setting so the impact of this research may be wider than only on academic work.
Sectors Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology

 
Description Tillingbourne Junior School, Science day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 120 7-year old children had a Science day organised for them by the school. Various play stations were organised, each dedicated to a biological concept. I was stationed at the microbiology one where we talked about microorganisms and how they grow and breathe. The children were very interested and knowledgeable showing great interest in science and the world around them.
Year(s) Of Engagement Activity 2019