New Hox Paper

Our work examining the selectivity of Hox transcription factor binding in a model cell line system reveals that much of the specificity is driven by chromatin accessibility and the ability of some Hox proteins to bind in closed chromatin. Great collaborative project with Rob White, with excellent experimental and analytical work from Damiano Porcelli and Bettina Fischer. Out now on bioRxiv

Spider Sox

Had great fun last summer in the McGregor Lab in Oxford-Brookes looking at spider Sox. Particular thanks to Chris and Alistair. The result was 2 BioRxiv preprints check them out here:

Paese CLB, Schoenauer A, Leite DJ,  Russell S, McGregor AP.  (2018)  A SoxB gene acts as an anterior gap gene and regulates posterior segment addition in the spider Parasteatoda tepidariorum. bioRxiv doi.org/10.1101/298448     Now published in eLIFE

Paese CLB, Leite DJ, Schoenauer A, McGregor AP, Russell S. (2017) Duplication and divergence of Sox genes in spiders. bioRxiv doi.org/10.1101/212647 

New(ish) students

Olimpia Bompadre and Maria Ouvarova join the lab for a Sox MPhil and Fat flies PhD respectively. Maria is working on a joint project with Jules Griffin and Kathryn Lilly in Biochemistry. Maria has been in the lab for a while but I’ve beed tardy in updating the website 🙁

Cambridge Beer Fest

It’s summery at the 44th Cambridge Beer Festival 🙂

New Chromatin Paper

Our new paper with Rob White’s lab on the organisation of the fly genome into H3K27me3 deleted and enriched domains  will appear in PLoS ONE shortly. Preprint is available from BioRxiv 

Alex Post viva and farewell

We bade farewell to Alex after he successfully defended his PhD thesis on Friday. Thanks for all your efforts Alex and best wishes for your future – in the meantime, enjoy Chinese New Year at home.

Stefan joins the lab

IMG_0455

We are excited to have Stefan Koestler  join the group  to work on our BBSRC funded project exploring the specificity and redundancy of fly Sox proteins.  After a PhD and Postdoc at the Institute of Molecular Biotechnology in Vienna where he did some excellent work on the cell biology of lamellipodia, Stefan spent 4 years in the Department of Molecular Biology and Genetics, Bogaziçi University Istanbul where he was working on Fly photoreceptor differentiation. Stefan has expertise in molecular biology and considerable experience with static and real time imaging at the cellular level. Here are a couple of his papers you can enjoy.

Koestler et al (2015).  FlyOde – A platform for community curation and interactive visualization of dynamic gene regulatory networks in Drosophila eye development.
F1000Research, 4:1484; WWW resource: http://flyode.boun.edu.tr/ 

Koestler et al 2013. Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilin.  Mol Biol Cell. 24(18):2861-75.

More Soxy birthdays

PBB_Protein_SRY_imageHot 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.

Happy Birthday Dichaete

Dichaete2It’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.
Sox_PCR

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 !

 

 

 

 

 

 

 

Dichaete3

 

 

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.

 

 

 

 

 

Dichaete4

 

 

My only single author research paper showed that ectopic expression of the Sox protein led to dominant wing hinge phenotypes

 

 

 

 

 

Dichaete_map

 

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

  1. Russell SRH, N Sanchez Soriano, CR Wright and M Ashburner (1996).  The Dichaete gene of Drosophila melanogaster encodes a SOX-domain protein required for embryonic segmentation.  Development122: 3669-3676.
  2. Sanchez Soriano N and S Russell (1998).  The Drosophila SOX-domain protein Dichaete is required for the development of the central nervous system midline.  Development 125: 3989-3996.
  3. Sanchez Soriano N. and S Russell (2000) Regulatory mutations of the Drosophila Sox gene Dichaete reveal new functions in embryonic brain and hindgut development.  Dev Biol  220:  307-321.
  4. Russell S.  (2000) The Drosophila dominant wing mutation Dichaete results from ectopic expression of a Sox-domain gene.  Mol. Gen. Genet 263: 690-701.
  5. Overton PM, Meadows LA, Urban J and S Russell. (2002) Evidence for differential and redundant function of the Sox genes Dichaete and SoxN during CNS development in Drosophila. Development 129: 4219-4228
  6. McKimmie C, Woerfel G and S Russell (2005) Conserved genomic organization of group B Sox genes in insects.  BMC Genetics. 6: p26.
  7. Phochanukul N. and S Russell.  (2010) No backbone but lots of SOX: the invertebrate SOX family.  Int. J. Bioch. Cell Biol. 42: p453-464
  8. Shen SP, Aleksic J, Russell S (2013) Identifying targets of the Sox domain protein Dichaete in the Drosophila CNS via targeted expression of dominant negative proteins. BMC Dev Biol 13: 1.
  9. Aleksic J, Fischer B, Ferrero E, Russell S. (2013) The role of Dichaete in transcriptional regulation during Drosophila embryonic development. BMC Genomics 14: 861
  10. Ferrero E, Fischer B, Russell S (2014) SoxNeuro orchestrates central nervous system specification and differentiation in Drosophila and is only partially redundant with Dichaete. Genome Biology 15:R74
  11. Carl SH, Russell S (2015) Common binding by redundant group B Sox proteins is evolutionarily conserved in Drosophila. BMC Genomics 16:292.

Sarah’s paper now out

 Sarah’s paper on comparative Sox binding is now available from BMC Genomics