The primary focus of my research is PROTEINS; their expression, folding, stability, binding interactions and catalytic activities, as well as different aspects of the science, design and engineering associated with the study of their forms and functions.
My approach is a "many questions, many subjects, many systems, many techniques" type of approach. I prefer it to the single protein, single question, single system, single techniques type of approach. You could say that this is a personal preference. To understand proteins in as many different ways as possible, and from as many different angles as I possibly can, I explore the gamut of protein qualities and behaviors, using multi-pronged, multi-faceted approaches.
I also contribute to the development of methods, molecules, processes, and technologies relating to proteins, and to the training and tutoring of younger researchers, as well as to some research administration.
With proteins, the line dividing fundamental science from applications is very, very thin. My research group and I cross this line in both directions, quite often. About seventy-five percent of the work that we have done is already published or patented; the rest is in the pipeline.
You are welcome to explore this website and enjoy reading up on what we do.
This was a hypothesis paper. At one time, I wondered how replication and transcription occurring on the same DNA template manage to deal with each other, in a bacterial genome. The possibility that the machineries for replication and transcription can collide (and the consequent delays involved in resolving such collisions) suggested to me that it would be much more convenient for a designer of a bacterial cell to organize for most genes to transcribe immediately after the passage of a replication fork, rather than in the path of a replication fork, so as to keep the numbers of such collisions to a bare minimum. When I began thinking deeply about this, a number of supporting arguments suggested themselves. For example, it seemed as if the induction of transcription by replication would provide an interesting correlate for the conservation of gene order in the genomes of bacteria occupying similar ecological niches, if such replication-induced transcription could organize to run a bacterial ‘cell cycle’ consisting of low copy number proteins which are made in the sequence in which they are required during the growth and division of a bacterial cell. Another argument that suggested itself was derived from the likelihood that much of the DNA in any genome is buried away from the cytoplasm in a compact form and therefore unavailable for transcription. Since a replication fork could be expected to unravel the bacterial nucleoid and transiently expose DNA, for replication to occur prior to the repackaging (and re-burial) of such DNA again into daughter nucleoids, it would make sense for any normally-buried genes to be made to (or allowed to) exploit their brief exposure to the cytoplasm during replication to additionally also make some transcripts during their brief exposure. Of course, this argument would not apply to genes that are normally (and always) present on the surface of a nucleoid, where they are ready-and-willing to be responsive to conventional negative regulation through repressors, or positive regulation through activators, in an environmentally-sensitive and responsive manner. It did not escape my notice that if most genes in the genome were programmed to transcribe in response to replication, then the quantum of transcription encountered by replication forks in the form of either constitutively expressed, or regulated, genes could be controlled and kept identical in all cells, allowing their synchronous growth and division, for no other mechanism could organize for all cells growing in a culture to display the same division time. These (and other arguments) are presented in this paper to suggest that over ninety percent of the genes in the E.coli genome only ever express through induction by the passage of the replication fork. The paper also presents three interesting ideas for how a designer could organize to physically and mechanistically link replication to transcription, and one of these ideas which I have called ‘transient depression’ has actually been experimentally demonstrated by other groups in some bacterial systems. I had great fun thinking of these things and writing them up and then revising the paper through into publication. I did much of the thinking while I was working on the biochemistry of lens proteins during my Ph.D, and I wrote the ideas up during my postdoc at Cambridge.
