Citation | Steve Busby is distinguished for his work on the molecular mechanisms that regulate bacterial gene expression particularly with respect to transcription initiation and to the effects of nutrient availability. He has made an outstanding contribution to our knowledge of how different sequence elements at promoters are recognised by different parts of RNA polymerase, and hence, how promoter strength is determined. His research has provided clear proof that many transcription activators function by making direct contact with RNA polymerase, and it has also provided the first detailed molecular definition of an activating surface of a transcription regulator and the cognate contact site of RNA polymerase. Working with the cyclic AMP receptor protein (CRP), it was shown that an activator can have more than one activating surface, that the functional activating surfaces depend on the architecture of the target promoter, and that different activating surfaces have kinetically distinct effects on transcription initiation. In consequence, more is known about the mode of action of CRP than any other transcription regulator. Moreover, the CRP model has provided a framework for understanding the organisation of scores of other promoters. These include some very complex promoters that are regulated by two or more transcription activators, where the effects of different metabolic signals are integrated in order to elicit the appropriate transcriptional response. |