Collins Conference Room
  US Mountain Time

This event is private.

Catie Grasso (Oregon Health & Science University)

Abstract.  Lynn Margulis’ endosymbiotic theory postulated that the eukaryotic cell arose from the symbiosis of multiple bacteria over time, making it possible to create organelles, like the mitochondrion and the chloroplast, which make eukaryotic cells extremely efficient and able to be building blocks in multi-cellular life.  Symbiosis has also been shown in genetic algorithm programming and genetic programming to make it possible to solve problems that cannot be solved by a single program alone.  This observation suggests the possibility that symbiotic genetic elements, like transposons and retrotransposons, present in multi-cellular organism genomes have the potential to similarly drive complexity by managing the various functional elements present in the human genome and making it possible to use these elements in a way that supports complexity.  I will present in my talk an example of a symbiotic genetic element driving complexity in humans:  the enslaved transposon involved in VDJ recombination, which drives the rearrangements necessary to build the enormous number of immunoglobulins that allow the immune system to differentiate between self and non-self.  I will also talk about alternative splicing, a retrovirally derived system that facilitates the evolution of multi-domain proteins by allowing exons to be included and excluded in certain contexts.  The rest of my talk will focus on how these symbionts that manage to organize the complexity of the human genome, have the potential to drive genome instability when mutated, resulting in the gene fusions that drive cancers and the highly rearranged genomes that occur in metastatic cancer.  Selection pressures in cancer, favor genomes that are instable, since this allows for rapid evolution, especially of drug resistance, since genes can be easily amplified to evade drugs that target binding sites by overwhelming the amount of drug that oncologists can deliver reasonably through copy number increases.  On the other hand, recent observations have shown that genome instability may be a treatment opportunity, if we can apply drugs, like PARP inhibitors that make double stranded breaks in the genome and thereby have the potential to make the genome so unstable that the tumor cells die, rather than evolving rapidly.  In fact, based on large scale sequencing efforts, cancer researchers are beginning to believe that targeting genome instability may be as important as targeting specific protein binding domains.  In this talk, I will explore two mutations thought to drive genome instability, CHD1 loss in prostate cancer and synchromere loss in all cancers.  Cancer researchers are exploring these mutations as potential new avenues of treatment in a new push that has resulting from observations made during recent massive cancer sequencing efforts.

Research Collaboration
SFI Host: 
Cris Moore