What are the circumstances which led you to your work?

When I started to work as a postdoctoral fellow in M. Geof Rosenfeld Laboratory at Howard Hughes Medical Institute my main interest was focused on the specificity of transcriptional activation. During my first days in the lab Geof told me: "Ed, you can practically do whatever you want in my lab as long as it is an amazing idea. However, before you start you need to convince me of it." He was laughing saying it but he was also deadly serious about it. At the time I was puzzled whether coactivators of transcription are promoter-specific and whether acetylation-dependent chromatin remodeling is important to achieve such specificity. Together with my mentors and colleagues from La Jolla—Rosenfeld, Chris Glass, Joe Torchia, Bob McEvilly, David Rose, and others—we spent a lot of time discussing these problems and trying to figure out the way to address the question. That was very intense and stimulating.

  Can you describe the significance of this work for your field?

I have no doubts that understanding the molecular mechanisms controlling gene expression at the global level and cell reprogramming associated with achieving new cellular function is one of the major challenges in biological sciences for the next decade. Every cell of a multicellular organism contains the same genome. How is it possible that some genes are highly expressed in liver but not present in neuron and vice versa? How is it possible that the cells with exactly the same genetic makeup are capable of functioning as fibroblasts or neurons? Another important challenge is related to epigenetically regulated processes including DNA methylation or histone modification in response to environmental changes. These problems must be much better understood before we move the biological sciences into a new era. We have a good idea about the general principles of the mechanism of transcription. However, how it is possible that the same factor exerts different effects on the same promoter in different cells or during different stages of cell differentiation is usually much less understood. We have accumulated extensive knowledge regarding regulation restricted to a single promoter, but the real challenge is to understand how the sets of genes associated with the particular cell program are (up- or down-) regulated all together. Without understanding the complexity of the regulation of gene expression at the global level, we will not be able to fully comprehend processes such as development of multicellular organisms, or formation of experience-induced long-term memories in brain, or homeostasis or aging processes. Unraveling mechanism-controlling patterns of gene expression is very important not only from a pure scientific interest point of view but it is also imperative to understand the etiology of many diseases, including cancer and neurological disorders. Thus I believe that new discoveries in the field will come from well-funded medically oriented research programs.

I think I still have some time before I have to deal with this kind of question—I am the next generation. I believe that the key for successful research is an intellectually challenging and clearly stated hypothesis. It may not sound very original but it is very efficient strategy. I do not necessarily think that all excellent research has to hit the top in ISI Essential Science Indicators, but it is very important (and obviously nice) to know that other people read your papers.