The considerable debate/discussion on my twitter feed regarding HIF journals prompts me to post the 1st edition of Cool. This appeared on the Glasgow Genetics Department Fax machine in the summer of 1990, shortly before I left for Cambridge. It has been on my office wall ever since and acts as a timely reminder that it is not where you publish but what you publish that should matter. The full version in all its glory is here – Cool-Article
The advent of CRISPR-Cas9 based genome engineering has opened up many avenues for genome engineering in many organisms. A group of Drosophila researchers active in the field have published some guidance and recommendations for using gene drive systems based on our collective experiences. We highlight some of the potential problems, provide suggestions for using drive-based systems and call for transparency in the use of these systems in the laboratory. The consensus view of our group is available now in Science.
Hot on the heels of Dichaete’s 100th birthday, today sees the 25th birthday of the publications describing the identification of SRY, the founder of the Sox family. Work from the labs of Peter Goodfellow and Robin Lovell-Badge (working in human and mouse respectively) demonstrated that the gene on the Y-chromosome controlling mammalian sex-determination encoded a new class of transcription factors and Sox was born.
It’s Dichaete’s 100th Birthday today. Discovered by Calvin Bridges on 3rd July 1915: “Among the offspring of one such pair-mating, Bridges found a single female whose wings were extended at a wide angle and elevated (culture 1817, July 3, 1915). Besides the divergent wing character there was present also a bristle character. Only the two posterior dorso-central bristles remained, the two anterior bristles being entirely absent. These features were so sharply defined that it seemed probable that they were the result of mutation.” Bridges & Morgan (1923) Pubs Carnegie Inst 327:p128.
Rush forward to 1995 & we demonstrate that Dichaete encodes a Sox domain transcription factor that has since kept us in business for 20 years. An honourable mention has to go to Peter Koopman who first generated a PCR product using SRY primers from fly DNA we sent him (see below). Initially skeptical, we quickly found that the PCR fragment did in fact identify a single copy fly gene – as soon as I saw the 1st in situ expression patterns I fell in love and our work on Dichaete began. Thanks to Natalia Sanchez-Soriano, Paul Overton, Lisa Meadows, Carol McKimmie, Gertrude Woerfel, Stephan Ohler, Adelaide Carpener, Shi Pei Shen, Jelena Aleksic, Enrico Fererro, Sarah Carl and Josh Maher, along with the host of undergraduate project students who have worked on understanding the role Sox genes play in fly development over the years. Most of all, of course, Michael Ashburner, who unfailingly and generously supported our work for many years.
One of the things I love about working on the fly is the strong link with the history of Genetics. In the lab, and in many labs around the world, the direct descendants of the Dichaete chromosome from the single female Bridges found 100 years ago are still in use as a valuable 3rd chromosome dominant marker.
Peter’s original Polaroid of the PCR with Sry DNA binding domain primers
Note the same size band with human, mouse and fly DNA at the highest annealing temperatures – it’s very conserved !
When I did the 1st in situ hybridisations it was love at first sight! When we (simultaneously with John Nambu’s lab, who sadly died last year) showed it was required for segmentation and CNS development, my love of Sox was cemented.
My only single author research paper showed that ectopic expression of the Sox protein led to dominant wing hinge phenotypes
Dichaete turned out to be interestingly complex with extensive 3′ regulatory regions which we were able to map with the aid of dominant mutation breakpoints.
Here is a list of our Dichaete-related papers
Sarah’s thesis work on Dichaete and SoxN binding in different Drosophila species is now available on BioRxiv. Reveals the shared binding by both proteins is highly conserved.
Rob White and I are extremely happy to have been awarded a BBSRC research grant to study how Hox transcription factors achieve target specificity. We are currently looking for a Postdoc to join the project who has an enthusiasm for understanding the genome biology of this ancient class of transcription factors (see advert till 18th Jan).