Dr Kenneth McDowall

Dr Kenneth McDowall

Profile

Joined the academic staff of the University of Leeds in 1996 after postdoctoral at Stanford University, California.

Responsibilities

  • Pro-Dean for Student Education
  • Senior Lecturer

Research interests

Macromolecular and genetic interactions that regulated gene expression.

The principal focus of the laboratory is the functional analysis of key events controlling gene expression. Of particular interest are the mechanisms that regulate and determine the nature of RNA decay and processing in E. coli and antibiotic production in S. coelicolor. Synthetic oligonucleotide chemistry, mass spectrometry, electron microscopy and surface plasmon resonance are all used in conjunction with a wide variety of biochemical techniques, bacterial genetics and bioinformatics.

Current Projects

Structural and functional analysis of RNA decay

The cellular level of RNA transcripts is a major determinant of gene expression in all living organisms, and is controlled as much by the process of RNA decay as the initiation of transcription. Although it is well established that RNA decay is a highly regulated process and that the stability of transcripts in E. coli can extend over two orders of magnitude, an understanding of the molecular mechanisms that underlie this aspect of gene expression is only now beginning to emerge. Much of our work in this area focuses on RNaseE, an E. coli endoribonuclease that initiates the decay of many if not most transcripts, is required for rRNA processing, and is evolutionarily conserved. The functions of RNaseE also extend far beyond that of a simple ribonuclease: it serves as a platform upon which other enzymes involved in E. coli RNA decay assembly to form a complex called the RNA degradosome. One of the major challenges is to determine the relationship between the functions of the individual components and their close physical association. To provide a framework for understanding ongoing genetic and biochemical analyses of the degradosome, we are currently analysing the structural relationship of components using transmission electron microscopy, analytical centrifugation, and cross-linking studies.

We are also gaining new insight into the enzymology of the catalytic domain of RNaseE (and sequence homologues), the regulation of cleavage by ancillary domains of RNaseE, and the contribution of RNaseE activities to degradosome-function by studying the decay of modified RNA substrates that are synthesised using a combination of phosphoramidite chemistry and recombination techniques. The enzymology of the RNaseE family is being studied as part of a fully funded project that is being undertaken with Dr. Jane Grasby (University of Sheffiled). We are also investigating the extent to which control events mediated by RNaseE-like activities are evolutionarily conserved. This work is being done as part of a collaboration with Drs Alexander von Gabain and Vladimir Kaberdin Vienna Biocenter, Austria.

Global analysis of E. coli gene expression

In collaboration with Prof. Peter Stockley, we are using the latest gene array technology to study the impact on global gene expression of mutations that through structural and functional studies are known to alter co-operativity, sequence recognition, multimerisation or small molecule binding of transcription factors. We are also determining a stability profile for the E. coli transcriptome, which in turn should provide an unprecedented opportunity to examine the integrated regulation of transcription and mRNA decay and determine the influence of individual RNA-decay factors on the stability of each member of the E. coli mRNA pool. The above project, which is funded, involves continued collaboration with groups based outside Leeds including Prof. Martin Buck, Imperial College.

Transcriptional regulation during stress and development

Streptomycetes are mycelial prokaryotes that respond to environmental stress by producing survival spores via a complex development pathway and by synthesising complex macromolecular compounds many of which have been found to have antimicrobial activity. Indeed this group of microbes makes two-thirds of all the natural antibiotics that are used clinically as well as several drugs that are used in the treatment of cancer and parasitic infections. In collaboration with Prof. Simon Baumberg, we are investigating the mechanisms that regulate antibiotic production by Streptomyces coelicolor and its morphological development in response to phosphate starvation, which is the major nutrient stress faced by soil dwelling organisms. At present, we are using the power of genetics to identify key regulatory components; however, with the sequencing of the Streptomyces coelicolor genome nearing completion it should be possible to rapidly purify individual components and begin to piece together the molecular interactions (at both the structural and functional level) that underlie this rudimentary biological response.

Each research interest is currently supported by external funding from the BBSRC and the Royal Society.

<h4>Research projects</h4> <p>Any research projects I'm currently working on will be listed below. Our list of all <a href="https://biologicalsciences.leeds.ac.uk/dir/research-projects">research projects</a> allows you to view and search the full list of projects in the faculty.</p>

Qualifications

  • BSc, Edinburgh; PhD 1991, Glasgow.

Student education

Undergraduate project topics:

  • Cloning and expression of genes, and purification of protein complexes

Postgraduate studentship areas:

  • The analysis of gene regulatory networks (e.g. mRNA decay and processing, and antibiotic production) and protein:nucleic acid interactions using transcriptome and proteome analyses in hand with genetics and biochemistry

See also:

Teaching activities

Modules managed

BIOL5382M - Extended Research Project

Modules taught

BIOC1301 - Introductory Integrated Biochemistry: the Molecules and Processes of Life
BIOC3160 - Laboratory/Literature/Computing Research Project
BIOC3221/22/BIOL3210/MICR3211 B - ATU - Life of an RNA
BIOC3231/32/BIOL3211/MICR3212 d - ATU - Human-microbe interactions
BIOL2110 - The Power of Bacterial Genomics
BIOL2111/BIOC2301 - Integrated Biochemistry/Genetic Engineering
BIOL2301/03/MICR2320 - Intermediate Skills - BIOL/MICR
BIOL3306 - Biological Sciences Research Project
BIOL5294M - MSc Bioscience Research Project Proposal
BIOL5372M - Advanced Biomolecular Technologies
BIOL5382M - Extended Research Project
BIOL5392M - Bioscience MSc Research Project
BIOL5394M - Specialised Research Topics and Skills
BIOW5901X - Foundation module
BIOW5902X - Medicinal Chemistry and Drug Design
BLGY1232 - Introduction to Genetics
BLGY3110 - Applied Genetics
BMSC2120 - Scientific Skills

Academic roles

Pro-Dean for Student Education - Pro-Dean for Student Education from 1st Aug 2015 for 3 yrs

Committees

  • Chair of Faculty Taught Student Education Committee (Pro-Dean for Student Education)
  • Member of Masters Taught Student Education Committee (Pro-Dean for Taught Student Education (ex officio))
  • Member of Taught Student Recruitment Group
  • Member of Undergraduate School Taught Student Education Committee (Pro-Dean for Student Education (ex officio))

Research groups and institutes

  • Structural Biology
<h4>Postgraduate research opportunities</h4> <p>We welcome enquiries from motivated and qualified applicants from all around the world who are interested in PhD study. Our <a href="https://biologicalsciences.leeds.ac.uk/research-opportunities">research opportunities</a> allow you to search for projects and scholarships.</p>