The 2011 Novitski Prize: Abby F. Dernburg

EACH year the Genetics Society of America celebrates the achievements of the extraordinarily creative Drosophila geneticist Edward Novitski (1918–2006) by awarding the Edward Novitski Prize. This award, which is generously supported by the Novitski family, recognizes a corpus of research that has made major contributions to genetics by employing novel, ingenious, and highly creative approaches. This year that award goes to an extremely talented young geneticist, Abby F. Dernburg, an Investigator with the Howard Hughes Medical Institute, an associate professor in the Department of Molecular and Cellular Biology at the University of California at Berkeley, and a Faculty Senior Scientist in the Life Sciences Division of the Lawrence Berkeley National Laboratory. Throughout her career Abby has used an innovative and elegant fusion of genetics, cell biology, and high-resolution light microscopy to make major contributions to chromosome biology in both Drosophila and Caenorhabditis elegans. Indeed, it may be simply said that much of what we know about the mechanisms by which chromosomes find and pair with their homologs during meiosis comes from the work of Abby and the students and postdocs whom she has mentored.

During her Ph.D. thesis work with John Sedat at the University of California at San Francisco, Abby explored diverse aspects of chromosome biology in Drosophila, leading to new insights into the role of nuclear architecture in position-effect variegation (Dernburg et al. 1996a), the contribution of sperm dysfunction to non-Mendelian inheritance (Dernburg et al. 1996b), and a temporal understanding of how heterochromatic pairing can mediate meiotic chromosome segregation in female meiosis (Dernburg et al. 1996c). These studies were the equivalent of three Ph.D. thesis projects, any one of which would have been considered superb on its own. This enormous achievement was recognized by Abby's receipt of the Larry Sandler Memorial Award for the most outstanding thesis in the area of Drosophila genetics and biology from the Genetics Society of America in 1997.

Abby continued her efforts to develop cytological tools to marry genetic studies of chromosome biology with high-resolution cytology during her post-doctoral work on C. elegans in Anne Villeneuve's lab at Stanford. These efforts largely laid the foundation for the cytological analysis of pairing in this organism. In addition, her demonstration that synapsis in this organism did not require double-strand break formation (as it does in many other organisms) was a wake-up call to a community of meiotic biologists, since it firmly established that meiotic mechanisms might be more plastic and diverse than we might have expected (Dernburg et al. 1998).

However, Abby's most impressive accomplishments are embodied in her work on the mechanisms of chromosome pairing in C. elegans. Since she established her own lab in Berkeley, Abby has tenaciously pursued a long-standing mystery: the problem of how chromosomes find and synapse with their homologs during meiosis. The ability of each chromosome to find its homologous partner, recombine with it, and eventually segregate away from that partner is the core of the meiotic process. While many details of the mechanisms that underlie recombination and segregation have been elucidated, pairing has remained a near total enigma for a century since Barbara McClintock first posed the problem of homology recognition.

When you think about the problem of pairing, you realize that it is an example of that most fundamental of all biological problems: How does a biological entity like a chromosome, a cell, or even a person distinguish self from non-self? In the case of meiosis, how does one chromosome identify its homolog and, in doing so, discriminate against all of the other chromosomes in the cell? While this question remains incompletely understood, Abby's efforts have both constrained the way we think about pairing and developed the tools that will eventually let her solve this truly fundamental problem. In that sense, her accomplishments parallel those of McClintock and of Calvin Bridges, whose pioneering studies of meiotic chromosome biology and genetics redefined the field for generations to come.

Genetic analyses by Bob Herman, Ann Rose, and Anne Villeneuve established the existence of special regions on each chromosome in C. elegans, known as “homolog recognition regions” or “pairing centers,” which play essential roles in promoting meiotic recombination and segregation. Work in Abby's lab over the past decade has illuminated what these pairing centers do and how they do it. Early work from her lab revealed that pairing centers play separable roles in promoting homolog pairing and formation of the synaptonemal complex, which stabilizes interactions between homologs (MacQueen et al. 2005). Abby also uncovered a surprising role of pairing centers in a meiotic checkpoint that monitors chromosome interactions (Bhalla and Dernburg 2005).

But perhaps most critically, Abby discovered that pairing center function depends on a family of unusual zinc-finger proteins that recognize short, repetitive sequences that are enriched in these regions (Phillips et al. 2005, 2009; Phillips and Dernburg 2006). These proteins allow the pairing centers to interact with cytoplasmic microtubules and dynein via a nuclear envelope bridge containing the SUN/KASH domain proteins SUN-1 and ZYG-12 (Sato et al. 2009). This evidence has illuminated the initial steps in the process by which chromosomes move along the nuclear surface and encounter their partners. More surprisingly, it has suggested the existence of a “licensing” mechanism by which homologously paired chromosomes proceed to undergo synapsis. This dynein-dependent mechanism somehow enables meiotic cells to discriminate between inappropriate, or heterologous, contacts and proper homologous pairing. As Abby envisions it, this mechanism works by attempting to separate paired chromosomes and presumably acts to test the “strength” of their interaction and thereby assess whether they are proper partners. Abby's work has now begun to address the question of how these initial interactions at the pairing centers facilitate the process of full homolog synapsis. Her success with this problem required technical innovation in cell biology and microscopy as well as some simply elegant genetics and molecular biology.

In addition to her work on homologous pairing, Abby's group has also made extremely significant contributions in the areas of crossover control, the mechanism of synapsis, and the identification of a checkpoint that monitors proper synapsis (e.g., Bhalla and Dernburg 2005; Carlton et al. 2006). She has also trained a cadre of excellent students and postdocs. Finally, Abby is also a superb colleague who is so much more than generous in terms of her time, her energy, and especially her critical intellect.

Abby's efforts and successes have been recognized by more awards than there is space to list—most notably, an Early Career Life Scientist Award from the American Society for Cell Biology in 2007, the Presidential Early Career Award for Scientists and Engineers in 2004, and the Burroughs Wellcome Career Award in Biomedical Sciences in 2000. The Genetics Society of America is proud to add one more accolade to that list, the Edward Novitski Award. It is an honor as appropriate as it is richly deserved.

Figure 1.

Abby F. Dernburg