FASEB Summer Research Conference on Dynamic DNA Structures in Biology: Sergei Mirkin

As part of its mission to encourage engagement within the genetics community, PLOS Genetics is sponsoring a number of conferences and meetings this year. In order to raise awareness about these conferences and the researchers who attend them we are featuring a number of these conferences on Biologue, with posts written by the organizers or PLOS Genetics editors who are involved.

The next of these conferences is the FASEB Summer Research Conference “Dynamic DNA Structures in Biology”, which takes place in Itasca, Illinois between the 20^th and 25^th of July. We asked Sergei Mirkin, an organizer of the conference and Chair of Biology at Tufts University, about the meeting, and the aspects of dynamic DNA structures that he finds exciting.

Where are you from? What do you research? What is the conference about?

I am Sergei Mirkin, a Chair of Biology at Tufts University and organizer of the FASEB Summer Research Conference “Dynamic DNA Structures in Biology”. This topic is very close to my heart, since I have devoted most of my research career to it. During my Ph.D. training at the Institute of Molecular Genetics, Russian Academy of Sciences, I studied the role of DNA supercoiling in DNA replication and transcription in E. coli. At about this time, the paradigm that DNA is nothing more than a regular, right-handed double helix began to change following the discovery of left-handed Z-DNA by Andrew Wang and Alex Rich, and DNA cruciforms by David Lilley and Bob Wells. These developments ignited my interest in structural transitions in DNA.

During my postdoctoral years we, together with Victor Lyamichev and Maxim Frank-Kamenetskii, found a totally unexpected DNA structure, called H-DNA, the main element of which was intramolecular triple-helix. This was the first demonstration for the presence of multi-stranded structure in natural DNA! This striking finding was soon followed by the discovery of Dipankar Sen (a speaker at this conference) and Walter Gilbert that functionally important DNA motifs can form four-stranded, G-quartet DNA. Subsequently, more alternative DNA structures came to stage, including DNA Unwinding Elements (DUE) by David Kowalski, i-motifs by Maurice Gueron, mismatched hairpins by Cynthia McMurray (a keynote speaker at the conference), slipped-strand DNA by Christopher Pearson (a speaker at the conference) and Richard Sinden and others.

While these were exciting developments, the biological role for any of these structures remained completely unclear. A particularly challenging problem was the detection of these structures inside living cells. It took our community another decade or so to realize that, since formation of these structures requires extensive DNA strand separation, they are only transiently formed during the genetic transactions involving DNA unwinding, such as DNA replication and transcription, explaining the difficulties with their detection in vivo.  The term “dynamic DNA structures” was then coined to account for their transient nature.

More recently, we began to understand the biological consequences resulting from the formation of dynamic DNA structures in the course of major genetic processes. One of the most striking examples was the discovery that expansions of structure-prone DNA repeats leads to more than thirty hereditary neurological and developmental diseases in humans. Dynamic DNA structures are actively involved in normal genome functioning including transcriptional activation, regulation of antigenic switching and DNA recombination essential to the immune response.  At the same time, they were linked to chromosomal fragility and chromosomal translocations observed in human cancers and genetic diseases. In an unexpected twist, DNA structures appeared to be quite useful for nanotechnology, where their unusual physical properties find many applications.  Consequently, the interest in dynamic DNA structures is high and continues to grow with new discoveries of their biological roles, as well as their uses.  All these topics will be discussed at the proposed FASEB Dynamic DNA Structures meeting.

How did you come together to put on this conference? What are you hoping to accomplish over the few days?

The idea to organize a FASEB conference devoted to these structures first came to Alison Ratray and Susanna Lewis back in 2008: the prime focus of the first conference were DNA cruciforms and hairpins. The second conference with a broader focus on alternative DNA structures was co-organized by Alison, Susan and Nancy Maizels in 2010. In 2012, Nancy Maizels and myself co-organized the third one, which held its current name: Dynamic DNA Structures in Biology.  This year, I co-organize it with Sue Jinks-Robertson and Alain Nicolas. I really admire this forum, as it provides us with a flow of ideas and discussions on the role of dynamic DNA structures in various genetic processes. By everyone’s account these conferences have energized our field and have given us plenty of new ideas and experimental directions! I am therefore looking forward to spending a week at this exciting conference.

If you could collaborate with one scientist from any period of time, who would it be?

Francis Crick back in the 1950s/1960s. I cannot think of a scientist, who has made bigger contribution to molecular biology! There are two problems with this wish, however: (i) I had only just been born at that time, and (ii) even if I were grown up, Francis would probably kick me out for not being smart enough to catch up with him… In any event, I would love to give it a try!