Dr. Ben-Aroya's Lab
Dr. Shay Ben-Aroya is a Senior Lecturer in the Mina and Everard Faculty of Life Sciences. He came to Bar-Ilan University from the University of British Columbia, as part of the 2009 cohort of returning scientists, a special program within Bar-Ilan University to recruit young Israeli scientists to return to work in Israel.
Ben-Aroya and his team conduct advanced cancer research on the genetic level. Research in his lab focuses on the processes underlying genome stability.
In particular, the fundamental rationale that underlies their research is that chromosomal instability (CIN) is an important phenotype that contributes to tumourigenesis, and that the molecular basis of CIN is likely to be determined by studying the mechanisms of chromosome transmission in model organisms.
The general goal is to identify and characterize new functional determinants required for mitotic chromosome transmission in yeast and in mammalian cells, and to provide candidate genes for cancer predisposition and for novel therapeutic approaches.
Systems Biology: Understanding Chromosomal Instability
A significant number of eukaryotic genes and regulatory pathways have evolved to ensure that cells replicate and segregate their genomes with high fidelity and at the appropriate time.
However, when cells fail to adhere to these tight restrictions on their growth, the genome can become unstable. In the vast majority of malignancies, this instability, termed Chromosomal Instability (CIN), appears to involve gain and/or loss of whole chromosomes or large segments of chromosomes, which in turn leads to aneuploidy and/or gross chromosomal rearrangement. The molecular basis for this chromosomal instability has remained mysterious.
Ben-Aroya and has team conduct research on a model organism, the yeast Saccharomyces cerevisiae, to further understand the process of chromosomal instability.
Using a model organism to study highly conserved biological pathways, such as genome maintenance, can greatly facilitate functional discovery in humans. Additionally, the technical accessibility of the yeast Saccharomyces cerevisiae for advanced genetic and molecular analyses makes it an ideal organism for the study of CIN.
Ben-Aroya and his team aim to identify and characterize new functional determinants that are required for mitotic chromosome transmission in yeast and in mammalian cells. They will utilize genome-wide technologies to establish comprehensive physical and genetic interaction maps, which will serve as the basis for detailed mechanistic follow-up studies as well as for novel therapeutic approaches.
Novel Experimental Techniques
To study the function of each gene, scientists remove single genes from the DNA of cell cultures and investigate the differences in functioning between genetically deficient cells and normal cells.
However, this technique cannot be used for certain genes, such as those that are essential for the cell’s survival, because their removal causes the cell to die. Ben-Aroya has developed new experimental tools that circumnavigate this problem, and has succeeded in determining the functions of these essential genes that have, until recently, been difficult to study.
When a body cell replicates itself, a copy of its genome – the sum total of its genetic material – is passed down to the next generation. But in the case of cancer, cell replication is unstable.
Using yeast as a model, Ben-Aroya and his team map out the complex interactions that ensure genome maintenance and stable chromosome transmission in both yeast and in human body cells.
This work will allow them to identify specific genes that promote a predisposition for cancer, as well as molecular targets for novel anti-cancer therapies.
Looking to the Future
The work of Ben-Aroya and his group describes a direct path from identification and mechanistic understanding of CIN genes in yeast, to mining sequence data for orthologs mutated in cancer, to the investigation of the function of somatic variants.
Determining which mutations are drivers and which are passengers is one of the most pressing challenges in cancer genetics. Ben-Aroya and his team’s research approach will exploit the new list of essential CIN genes, to prioritise the missense mutations most likely to generate functional changes that enhance tumour cell proliferation and contribute to tumourigenesis (so-called “driver” mutations), and which are functionally less significant (“passenger” mutations).