Shaw Lab
School of Biomedical Sciences,
Medical School, Queens Medical Centre,
Nottingham. UK.

 About Our Lab - a Brief History 

Background

It's almost three years since the lab moved from Freiburg, in southern Germany, and set up shop in the Department of Biochemistry at Nottingham University's Medical School. But already the Department of Biochemistry has been superseded and the lab currently forms part of the School of Biomedical Sciences, a modern, multidisciplinary mélange, and the Institute of Cell Signalling, a University Flagship Enterprise. This apparently reflects the pace of progress in Britain's medical sciences these days.

The Lab is housed on the fourth floor of the Queen's Medical Centre. The windows have a southern aspect, offering splendid views that range from Radcliffe on Soar power station away in the west (which, thanks to its scrubbers, generates acid-free clouds) to Nottingham Castle, squat on its hill to the east, with the River Trent, partially visible, meandering murkily between them.
The city, spread out behind the castle, offers major attractions that allow Nottingham University to proclaim itself to be the most popular University in Britain: about fifty nightclubs, including Rock City, whose fame had reached even Freiburg along with Robin Hood's. Then there is Trent Bridge for the sporting connoisseurs and the City Ground for sporting masochists.

Science

Our endeavours continue to address two interdependent aspects of eukaryotic cell biology, the regulation of transcription and signal transduction mechanisms.

Transcription

As a model for inducible gene expression, the c-fos proto-oncogene has proven to be an interesting and popular paradigm. It is induced by a wide range of physiological agonists and nonphysiological abuses (such that only the discovery of something that doesn't elicit a response causes a raised eyebrow here). The rapid nature of this transcriptional response was first documented by Mike Greenberg and Ed Ziff, back in 1984.  Surprisingly it was not foreseen by George Orwell.

Somewhat to Mike Greenberg's chagrin, the baton was taken on by Richard Treisman who succeeded, almost single-handedly, in mapping the Serum Response Element (SRE) within the c-fos promoter and then identifying, purifying and cloning the Serum Response Factor (SRF), which binds to the SRE. SRF apears to be another saddle on the DNA, like the TATA-box Binding Protein (TBP). It even bends the SRE, which has an A/T rich core, albeit it in the opposite way to TBP.

At least one rider is known to sit on this saddle. It was identified initially as a 62kd polypeptide and was originally referred to as the ternary complex factor (p62TCF). TCF is probably a heterogeneous activity in most cells and in fact, to date, three genes have been identified, one way or another, that encode TCFs: Elk-1, Sap1a and Net/Erp/Sap2. The proteins are closely related and belong to the ets family of transcription factors.

Signalling

For those surfers who are bored by transcription, here comes the link (excuse the pun) to signal transduction: TCFs are phosphorylated by MAP kinases.

Ever since we found that out the Lab has been mildly schizophrenic as we tried to dance at two weddings. Anyway, the carboxy-terminal domain of Elk-1 (or Sap1a, or Net/Erp/Sap2 for that matter) is multiply phosphorylated by ERK1 and ERK2 in response to mitogenic signals, and by SAPK/JNKs and probably even p38mapk in response to noxious agents and cellular stress [for more information see Jim Woodgett's page].

So besides continuing to try and understand how TCFs actually get RNA polII rolling off the c-fos promoter once they become activated, we have also aimed to chart some of the pathways from the many agonists that influence TCFs. One of the approaches we have taken is to adapt TCFs so that various upstream signalling events can be monitored specifically and selectively.

 
Peter Shaw

last modified 22.09.11