Research Interests:

We are interested in understanding how the major evolutionary forces of mutation and natural selection lead to interesting outcomes such as the emergence of antibiotic resistance, the generation of phenotypic variation within bacterial populations, and cancer development within the human body.

Main projects in the lab:

1. Understanding the dynamics of antibiotic resistance acquisition in the absence of antibiotic exposure:  Mutations that confer resistance to antibiotics often occur within the genes targeted by the antibiotics, altering their structure to prevent the binding of the antibiotic. Since genes targeted by antibiotics tend to be important housekeeping genes, such mutations often strongly affect fitness even in the absence of any exposure to antibiotics. We and others have shown that the frequency of resistance to antibiotics increases when bacteria are starved, even when the bacteria are not exposed to antibiotics. We showed that such increases were not due to increases in mutation rate. Rather, they were due to some resistance mutations improving bacterial growth under starvation even in the absence of the presence of antibiotics. Such adaptive effects of antibiotic resistance mutations could greatly affect the dynamics of antibiotic resistance accumulation and spread. We are therefore continuing to study these mutations to understand the mechanism behind their adaptive effects, their frequencies within natural bacterial populations and how they are affected by selection under other growth conditions.
2. Studying Cancer by utilizing evolutionary approaches and insights: Cancer initiation and progression are short-term evolutionary processes that occur within our bodies. A great deal of progress in the understanding of cancer can therefore be gained by employing evolutionary insights. A great example of how the study of evolution can be directly applicable for understanding cancer is the example of identifying genes evolving under positive selection within tumors. The genetic variation that is necessary for evolution to move forward is generated by mutation. Somatic mutations are the type of mutations relevant for the cancer micro-evolutionary process within our body. This is in contrast to germline mutations that generate the variation needed for organismal evolution. Natural selection, together with other stochastic forces, determines whether mutations vanish from the population or whether they are allowed to persist. Natural selection acts in two ways: Purifying selection removes from the population mutations that are harmful to fitness, while positive selection increases the likelihood that adaptive (beneficial) mutations will persist. Somatic mutations subject to positive selection within tumors are of particular interest, as these are the mutations that contribute positively to transformation, tumor maintenance, expansion, drug resistance and metastasis. Therefore, by using evolutionary based approaches to identify positive selection acting within tumors we can identify key genes and pathways important for cancer.  We have developed a new method for the detection of positive selection acting on groups of genes within tumors. We used this approach to demonstrate that within tumors genes that are expressed globally across tissues tend to be enriched for positive selection. We further showed that many such globally expressed genes that have not yet been associated with cancer are subject to positive selection within tumors, and are therefore important for the cancer phenotype. We are currently expanding our approach to detect individual genes subject to positive selection within tumors. This will allow us to identify individual cancer-driving genes, which is a major aim of cancer genomics.
3. Studying the dynamics of bacterial evolution via changes in gene content: using both data of sequenced bacterial genomes and metagenomic data we study how changes in gene content contribute to the evolution of microbes, including such important pathogens as Mycobacterium tuberculosis
4. What determines variation in nucleotide and codon-usage among microbes? Nucleotide content as well as codon usage vary greatly between different microbes. The reasons behind this variation remain elusive. We use a variety of computational approaches to study the evolutionary reasons for this great variation
5. How does the fresh-water microbiome affect water quality and how is water quality in turn affecting the microbial communities contained within water sources?  In past years it has been made clear that the bacteria that inhabit the human body greatly affect and are greatly affected by human health. We are trying to determine whether and how the “health” of water sources is also so affected by the microbial communities contained within water sources across Israel.  Major questions of this study include: what are the structures of microbial communities contained within different Israeli fresh-water sources? how do these structures relate to different parameters of water quality?, and how do these structures relate to the presence of antibiotic resistance determinants and toxins within water sources?. This is a highly collaborative project involving six research groups, from many research institutions across Israel, with various expertise (marine biology, ecology, chemistry, genomics, computational biology, microbiology).

 Are there any open positions in the lab?

Yes, we are currently looking for a highly motivated student to work on project number 5 described above. This project is collaborative and highly interdisciplinary in nature, involving ecological field work, lab work and extensive sophisticated bioinformatic analyses of both genomic and metagenomic data. The student involved will gain a variety of expertise and will be front and center in what is shaping up to be a very exciting project. This student will be co-advised by Dr. Daniel Sher from the Marine Biology program of the University of Haifa and by me. For more details please email me at: ruthersh@tx.technion.ac.il.

 Lab website: http://hershberg.net.technion.ac.il/