Nancy Kleckner, Herchel Smith Professor of Molecular Biology, looks back at crucial moments in her career in a Nature Cell Biology Turning Points essay (PDF)—from becoming enthralled with the structure of DNA as a high school student in California to studying the behavior of the genetic material in the context of whole chromosomes.
The Turning Points series found in Nature journals invites esteemed researchers to compose essays “describing pivotal events in [their] careers,” according to Nature. Kleckner’s article, “From Phage Genetics to Chromosomes as Mechanical Objects,” appears in the July 20 issue of Nature Cell Biology.
As Kleckner describes in her article, her research has progressed from bacterial and bacteriophage genetics through mechanistic biochemical analysis of transposable elements to current work that investigates E.coli nucleoid dynamics, pairing and recombination patterning along organized meiotic chromosomes, and roles of mechanical forces in mitotic chromosome morphogenesis. She warmly acknowledges key inputs from her Harvard BMB/MCB colleagues in her evolution as a scientist, throughout her journey, from undergraduate studies to the present day.
Kleckner adds that her work in all of these various areas has been united by two themes.
“First, we try to identify a process of interest and then ask, ‘how could it work?’” she says. “Second, it is a basic feature of science that if you apply a new methodology, you will make new discoveries. Thus, I have always tried to provide an environment in which the members of my laboratory can use their talents to invent new approaches. This is exemplified by current work of Dr. Maria Mukhina, who is developing nanoscale tools for fluorescence imaging detection of mechanical stress patterns in living cells.” This new tool can be combined with functional analyses in normal situations, and the effects of mutations in molecules expected to sense and transduce stress. Such studies will allow direct demonstration and analysis of the nature and roles of mechanical stress in a broad variety of biological contexts over a wide range of length scales. Examples include spatial patterning and morphogenesis of chromosomes, the role of membrane tension (e.g. on the catalytic activity ecto-ATPase CD39 as envisioned by Guido Guidotti) and complex systems such metastasizing cancer cells, developing tissues or the beating heart.