Recent advances in genome engineering technologies based on the CRISPR-associated RNA-guided endonuclease Cas9 are enabling the systematic interrogation of genome function. Using this system, DNA sequences within the endogenous genome and their functional outputs can be easily edited or modulated. Cas9-mediated genetic perturbation is simple and scalable, empowering researchers to elucidate the functional organization of the genome at the systems level and establish causal linkages between genetic variations and biological phenotypes . Recently, application of CRISPR/Cas9 system has become popular for therapeutic aims such as gene therapy.
We are using this platform to define a map of druggable genetic dependencies/essentialities across a number of selected cell lines; some of which are expected to be clinically actionable with currently available small molecules or other drugs. In parallel, we are seeking to understand molecular pathways that control expression of proteins involved in carcinogenesis and/or immune system evasion by tumours.
Screening and gene editing technologies are used to screened for therapeutic modulation targets in human primary cells. CSHM scientists are looking for targets to control activation of immune responses in disease settings such as cancer. Primary cell screening, includes isolation of cells of interest of hematopoietic or non-hematopoietic origin and in vitro culturing and/or expansion. The ability to scale-up the expansion of cells is a major challenge in cell therapy. Scientists are establishing a variety of culturing protocols to support the expansion of various cell types. Currently, there is a focus on conventional T cells, regulatory T cells and NK cells.
The importance of genomic data in medicine has been ever increasing especially in the field of cancer biology and treatment decision for cancer patients. The use of next-generation sequencing (NGS) technologies has been a revolutionizing advancement in providing such information and at a timely manner for use in the clinic.
CSHM scientists are working to provide a high-throughput genomics platform for the biosciences community. This will include support and experimental design and advice, NGS library preparation methods, DNA extraction, long-read sequencing, long mate-pair library construction and exome capture, analysis from transcriptomics to exome sequencing, genome assembly, genome annotation and metagenomics.
NGS can often create large datasets that pose a computational challenge. The Center will provide a genome analytics solution by enabling high-performance computing support.
The development and widespread use of multi-omics has made imperative the use of bioinformatics. Bioinformatics allow scientists to gain a deeper and wider understanding of biological processes by analysing big datasets that are otherwise impossible to analyse. Major research efforts in the field include DNA/RNA/protein sequencing, sequence alignment, gene finding, genome assembly, drug design, drug discovery, protein structure alignment and prediction, prediction of gene expression and protein-protein interactions, genome-wide association studies, and the modelling of evolution. Equipped with advanced computing instruments and software, CSHM scientists will provide support to the broader research community of the region.
In collaboration with local and international partners and taking advantage of its close association with its parent organisation Karaiskakio Foundation, the CSHM is working on establishing xenograft tumour models from patient-derived tumour tissue (PDTT). Patient-derived xenografts are believed to offer relevant predictive insights into clinical outcomes when evaluating the efficacy of novel therapies.