David Miller

Profile

Having completed my PhD in dental biochemistry in 1982, I went on to study cell cycle proteins and microtubule dynamics in the slime mould, Physarum before moving to Liverpool University. There, I began a career-long interest in heat shock proteins and their ability to protect cells against environmental stress. Initially, this work used the eggs and larvae of the brine shrimp Artermia salina (the eggs are very tolerant to desiccation), which I continued following my appointment as senior lecturer in biochemistry in Liverpool John Moores University 

Research interests

I am interested in the molecular and genetic aspects of male infertility and reproductive function and the underlying causes of male factor infertility and reproductive dysfunction, the great majority of which, has unknown causes. Using wholly non-invasive methods that make use of ejaculate spermatozoa, we are compiling an RNA database that describes the fertile male and comparing this with RNA profiles obtained from the semen of infertile men. In this way, we aim to identify gene expression pathways that are affected in the infertile male. At the same time, if we know what RNAs are present in the spermatozoon, we can identify, by comparison with the RNAs that are present in the egg, those that are specific to and delivered by the sperm. Once we have identified these 'male' specific messages, we can begin assessing whether they have any function or influence on the developing embryo. In a similar vein, we are looking more closely at how chromatin is packaged in the spermatozoon. So far we have found that DNA in human and murine spermatozoa is packaged by a mixture of histones (as is the case with all somatic cells) and protamines (peculiar to spermatozoa). More interestingly, we have important evidence that different regions of the DNA are differentially packaged into these two compartments such that genic regions are enriched in the histone bound regions. This has important implications for male fertility because it suggests that some important stretches of DNA in sperm chromatin, containing particular gene sequences may be more susceptible to intrinsic or externally regulated damage, leading to sperm dysfunction. See Saida et al, 2011 and Arapanhi et al, 2009. 

I was closely involved in the REPROTRAIN International Training Network, coordinated by Rafael Oliva in Barcelona with three projects based in Leeds. Two projects provided training for Early Stage Researchers (ESR) to undertake research in the composition and packaging of human and bovine sperm chromatin. With a focus on sperm quality based on both differential density gradient centrifugation and the ability to bind hyaluronic acid, one of these projects (ESR1) examined the RNA composition of 'competent' and 'incompetent' sperm using a combination of microarray and second generation RNA sequencing. Both mRNAs and miRNAs were investigated as part of this project and aspects of sperm RNA and protein turnover and synthesis on mitoribosomes were explored. A second ESR post looked at differences in DNA composition of histone packaged DNA in 'competent' and 'incompetent' sperm again focusing on their sedimentation characteristics and hyaluronan binding properties. We were particularly interested in exploring the relationship between sperm quality and histone retention, with regard to differential DNA packaging (into histone and protamine binding domains) and the work will also involve a combination of microarray and second generation DNA (exome) sequencing. Localising chromatin domains in sperm nuclei. A third post for a more experienced researcher (ER) explored the use of seminal plasma as a surrogate for assessing prostate health (ranging postatic intra-epithelian neoplasmia or PIN to full Gleason 7 prostate cancer and we are developing an RNA-based diagnostic for this purpose. 

Student education

MSc Clinical Embryology: Module leader for Module 1 in Fundamentals of Clinical Embryology and Module 6 Research Proposal.

MSc Lifestyle, Ageing and Reproductive Health: Programme manager and module leader of Module 1 (Fundamentals of Clinical embryology-1), Module 2 (Fundamentals of Clinical embryology-2) and Research Module.

Module in Molecular Human Reproduction for intercalated BSc in Clinical SciencesReader in Molecular AndrologyRecent Projects 

Research groups and institutes

  • Leeds Institute of Cardiovascular and Metabolic Medicine
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