Our society faces enormous interdependent biomedical challenges: cancer, antibiotic resistance, and unbalanced human microbiomes, to name a few. In cancer, somatic mutations make the tumor of a given patient to evolve toward a mixture of multiple genotypically and phenotypically distinct cell populations. This contributes to failures in targeted therapies and to drug resistance. The overuse of antibiotics has accelerated the rate at which bacteria evolve resistance by spontaneous mutations or horizontal gene transfer. On top of that, it has left many people with an underdeveloped microbiome—the community of bacteria and viruses living in our gut, skin, and mouth.
These major shifts in microbial community composition are often associated with ill health, because the long-term stability of the microbiome is considered critical for our well-being. Moreover, recent evidences for cancer patients suggest that the gut microbiome helps determine whether tumors shrink when treated with immunotherapy drugs. For this reason, researchers are now planning clinical trials to test whether manipulating the gut microbiome with fecal transplants could improve cancer treatment.
Scientists are currently working on alternative smart solutions to those challenges: linage tracing techniques to cancer as a possible avenue to uncovering and fully characterizing ecological and evolutionary dynamics within the tumor, using bacteriophages—phages—that selectively kill antibiotic resistant bacteria (phage therapy), and engineering interactions among bacteria and between bacteria and viruses within our bodies to treat the human microbiome. Yet, this is still a long way off.
On the one hand, current technology does not allow us to characterize the genoytpes of thousands of cells per generation—still less to determine with certainty their ancestor-descendant relationships. Nor synthetic genomic approaches have yet reached the state where synthesizing and engineering bacteriophages from scratch is routine. On the other hand, we are still trying to infer the interactions that take place between the microbes living in our bodies.
Once we overcome those titanic endeavors, that is, being able to forecast the evolutionary trajectories of populations of malignant cells, design and develop phages from scratch, and have our microbiomes sequenced and characterized regularly, we will need a framework to understand the evolution and coevolution of multiple coexisting clades of malignant cells, antibiotic resistant bacteria and their phages, and bacteria that compete and cooperate among each other and that are killed by phages within our microbiomes.
We belive the time to develop a general approach to harness the evolution of asexual populations of malignant cells, pathogens, and entire microbial communities is now. This is why our computational biology lab focuses on harnessing evolution by engineering species interactions to help fight human diseases.