NetherlandsCountry of destination:
Understanding the epigenetic mechanisms in host-pathogen systems is a critical prerequisite to prediction and development of mitigation strategies for any disease. In this project, we propose to investigate the implication of epigenetic phenomena in influenza virus infection. During the first project phase, we will use in vitro and in vivo to evaluate whether the epigenetic status of infected cells and host cells is modulated during influenza infection. For this purpose, histone modifications such as acetylation and methylation, and DNA methylation will be analyzed during the course of infections. For histone modification quantifications, mass spectrometry analyses will be carried out for in vitro infections. For in vivo infection, chromatin immune precipitations and DNA microarray hybridizations will be performed to characterize modulation of the epigenetic status of the immune cells. During the second project phase, we will determine if epigenetic phenomena interfere with virus replication.
Towards this end, epigenetic enzymes inhibitors (targeting histone deacetylase and DNA methyltransferase) will be used to quantify their effect on virus replication. These studies will be completed by using specific siRNA targeting these enzymes to inhibit their expression and quantify their effects on virus replication. Furthermore, cells knockout for two DNA methylases (DNMT1 and DNMT3b) will be used to determine their role in the virus cycle. Our third objective will be to determine whether epigenetic phenomena induced by infection could contribute to acquired protective immunity. For this purpose, adequate mouse infection models and epigenetic enzymes inhibitors will be used.
My specialty is on molecular virology, biochemistry and vector biology.. I obtained my PhD degree at 2012 from Wageningen University, The Netherlands on functional genomics of a model invertebrate iridovirus using well-established Drosophila model system. I have a keen interest to be at the frontier of genomic research on the pathobiology of human viruses in this stage of my career. During my postgraduate research, I gained experience in genomics, transcriptomics, proteomics, infectomics and interactomics of large DNA viruses, notably in unique viral-host models to understand global pattern of DNA virus infection (infectomics) using Tsetse and Drosophila. With this regard, I have implemented an experimental Drosophila fly model system for a quantitative temporal proteomic approach; to identify proteins and pathways regulated in the host by viral infection e.g. immune response. The main focus of my ‘omics and system biology studies is to identify essential host cell factors in virus infection to contribute to the development of novel intervention strategies for viral infections, a topics that I developed in influenza model during my AgreenSkills fellowship. Currently, I am focusing to implement in silico approaches to delineate the complexity of microbiome-host interaction and unravel their impact on the microbial pathogenesis to provide the scientific basis for the development of novel bio-strategies and designing of bio-processes of products of a wide spectrum of interest in bio-industry.
Ikbal Agah Ince, Gorben Pijlman, Just M. Vlak, Monique M. van Oers, 2017. Hairpin structures with conserved sequence motifs determine the 3' ends of non-polyadenylated invertebrate iridovirus transcripts, Virology, 511:344-353, 2017.
V. Gregory Chinchar, Paul Hick, Ikbal Agah Ince, et. al. and ICTV Report Consortium, 2017. ICTV Virus Taxonomy Profile: Iridoviridae, Journal of General Virology, 98, 890-891, 2017.
Henry Muriuki Kariithi, Ikbal Agah Ince, Sjef Boeren, et al., 2016. Comparative analysis of salivary gland proteomes of two Glossina species with differential hytrosavirus pathologies. Front Microbiol., 7:89. Doi: 10.3389/ fmicb.2016.00089.
Adly M.M. Abd-Alla, Henry M. Kariithi, François Cousserans, Nicolas J. Parker, Ikbal Agah Ince, Erin D. Scully, Sjef Boeren, Scott M. Geib, Solomon Mekonnen, Just M. Vlak, Andrew G. Parker, Marc J. B. Vreysen, Max Bergoin. 2016. Comprehensive Annotation of the Glossina pallidipes Salivary Gland Hypertrophy Virus from Ethiopian Tsetse Flies: A proteogenomics Approach. Journal of General Virology, 97: 1010-1031.
Ikbal Agah Ince, Sjef Boeren, Monique M. van Oers, Just M. Vlak., 2015. Temporal proteomic analysis and label-free quantization of viral proteins of an invertebrate iridovirus. Journal of General Virology, 96: 196-205.