Friends and colleagues of Professor Dame Louise Johnson will be very saddened to learn that she suffered a serious and very incapacitating heart attack with complications in August 2011 and has been in hospital since then. Louise is visited daily by members of her family, and, starting very recently, by a small number of friends. Cards and messages can be sent to Louise c/o The Administrator, Department of Biochemistry, South Parks Road, Oxford, OX1 3QU, from where they will be passed on to the family and communicated to Louise.

Louise's research is documented as follows:

I retired from the University in October 2007 but retain my interests in protein kinases and their regulation in health and disease with special focus on the kinases involved in the regulation of the cell cycle, where the structure of Cdk1/cyclin B is a long-outstanding target being addressed by Jane Endicott and Nick Brown and in transcription where our structure of Cdk9/cyclin T (P-TEFb) has led to a programme on structure based drug design by Sonja Baumli, who is also addressing the higher order assemblies that regulate this kinase. My latest interests arising from my association with Diamond Light Source are in the applications of coherent diffraction imaging of cells and macromolecular assemblies and the exploitation of free electron laser X-ray sources.

P-TEFb (CDK9/cyclin T) promotes mRNA transcriptional elongation through phosphorylation of elongation repressors and RNA polymerase II. In order to understand the regulation of a transcriptional CDK by its cognate cyclin we determined the structure of the CDK9/cyclin T1 (CDK9/CycT1) (Baumli et al, 2008).

There are distinct differences between CDK9/CycT1 and the cell cycle CDK, CDK2/CycA, manifested by a relative rotation of 26° of CycT1 with respect to the CDK, showing for the first time plasticity in CDK cyclin interactions (Figure 1). Flavopiridol is an anti-cancer drug in Phase II clinical trials for chronic lymphocytic leukaemia and other cancers. Structural studies showed that flavopiridol bound to the ATP site of CDK9 inducing unanticipated structural changes that bury the inhibitor, providing specificity and potency (Figure 2).

The eukaryotic cell cycle involves replication of the genetic material and the cell's biomass to yield two duplicate daughter cells. Progression through the cycle is driven by the sequential activities of different cyclin dependent protein kinases (CDKs). The organisation of both the temporal and spatial events is characterised by selection of the right substrates by the protein kinases. CDK2/cyclin E governs entry into S phase during which DNA replication takes place. Levels of cyclin E are elevated in breast cancers. Structural studies on CDK2/cyclin E gave an explanation for some of its important cell properties (Honda et al., 2005). With CDK2/cyclin A we have sought to understand how the binding of a substrate at a remote site from the catalytic site can influence substrate specificity (Cheng et al 2006) (Figure 3). This has led to an investigation of how the different cyclins confer substrate specificity on their kinases. We have shown that although CDK2/cyclin A and CDK2/cyclin E have very similar properties the association of CDK2 with cyclin B confers different substrate recognition properties that are related to the role of cyclin B in mitosis (Brown, NR et al. Cell Cycle, 2007).