I am a lecturer in Medical and Forensic Genetics . I graduated with an Honours degree in Genetics from the University of Edinburgh in 1982 and shorlty after that I took up a job as a Scientific Officer with the South African Institute for Medical Research (SAIMR), which is affiliated to the multi racial University of Witwatersrand (Wits) in Johannesburg. Initially I worked for the Human genetics dept where I completed a part time Mres degree on X linked human genetic diseases such as Duchenne Muscualr dystrophy, X linked retinitis pigmentosa families. I also was in charge of the Tay Sachs carrier disease screening in the large Ashkenazi Jewish population in Johannesburg where approximately 1 in 30 are carriers of this early onset fatal disease. I also took an interest in Anti -Apartheid politics and lectured on the unscientific basis of it from a Human Geneticist's poit of view i.e.All humans are related and of African tribal origin. I later swithed from Human Genetics to the Deparment of Haematology, SAIMR/Wits Uni at the Johannesburg General hospital, where I helped set up a DNA test for diagnosing B cell and T cell leukemias by detecting clonal immunoglobulin and T cell receptor gene rearrangements.
In 1988 I was offered a PhD position at Newcastle University, back in the UK, working with Prof Shomi Bhattacharya onseveral large Autosomal dominant retinitis pigmentosa (ADRP) families of unknown genetic origins. I was lucky enough to be the first in the world to demonstrate that ADRP was multigenic and later helped identify several of the mutations in the Rhodopsin gene that was the underlying cause of the disease in some of the families. In 1991 I then moved back to my home city of Edinburgh to the MRC human genetics unit in Edinburgh to worlk on X linked Retinitis pigmentosa families
In 1994 moved again to the Roslin Institute just outside Edinburgh which was then based in the village of Roslin. Initially I worked on Cattle genetics, but soon switched to the bone/chondrocyte chicken development group under Prof Colin Farquharson. There I cloned and helped identify several novel genes including a human ubiquitin conjugating enzyme (UBE2J1 ) which is responsible for helping degrade both the Cystic fibrosis causing protein (CFTR) and helping the Parkin degrade several protein substrates involved in Parkinson's disease.In 1999 I then obtained Wellcome Trust money to work on 3 lines of blind chickens at the Roslin Institute which are animal models of Humen retinal degeneration and dysfunction e.g. Congenital stationary night blindness and Retinitis pigmentosa
In January 2000 I left the Roslin Institute to take up a post as a Genetics lecturer at Abertay, but kept my research going at the Roslin Institute and was involved in identifying the genes underlying the blindness of two of the chicken lines. One of the chicken lines proved to also have kidney abnormalities and later with my then PhD student Hemanth Tummala found that the aberrant gene was GNB3 a gene involved in hypertension in humans, I then switched my research to studying this genes involvement in the disease and have invented a possible novel therapy for half of all humans who carry the GNB3 predisposition alllele.
I have sucessfully supervised 2PhD students. I am going to be supervising 1 MRes student who is starting in January 2012, to do some more proof of concept experiments on a ongoing patent application I have submitted. As a medical geneticist and DNA specialist with 30 years practioner experience I primarily teach Biomedical Scientists. However I also help teach the genetics of behaviour and the current future application of DNA technology in forensics, to forensic students and forensic psychobiology students respectively.
LSC403 Advanced Medical Genetics
LSC402 Honours Project (offering both BMS and Forensic projects)
Module Code : BI0803A£
Module Title : Molecular & Cell Biology 2a Introduction to Genetics
Module Code : BI0806A*
Module Title : Techniques and Skills 2b
Module Code : BI0911A*
Module Title : Applied Molecular and Cell Biology
Module Code : BI1003A£
Module Title : Contemporary & Industrial Biotechnology & Biomedical Science
Module Code : BI1004A
Module Title : Contemporary & Industrial Biotechnology & Biomedical Science
Module Code : BI1005A%
Module Title : Techniques and Skills 4
Module Code : BI1006A%
Module Title : Honours Project
Module Code : BI1008A$
Module Title : BMS Honours Project
Module Code : BI1009A$
Module Title : Project Skills
Module Code : BI1101A%
Module Title : Perspectives of Biotechnology
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Module Title : Analytical Biotechnology
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Module Title : Industrial Biotechnology
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Module Title : Biotechnology Case Review
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Module Title : Research project (MSc Biotechnology)
Module Code : BI1107A $
Module Title : Investigative Research Project (MSc Biotechnology)
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Module Title : Medical Biotechnology Research Project
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Module Title : MSc Bioinformatics Project & Dissertation
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Module Title : Molecular Techniques
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Module Title : Structural and Functional Genomics
Module Code : BI1119A*
Module Title : Introduction to Bioinformatic Techniques
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Module Title : Molecular & Cellular Biology 5: Genome Structure & Function
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Module Title : Demography
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Module Title : Forensic Applications of DNA
Module Code : FS1007A$
Module Title : Forensic Science Honours Project
Module Code : HS0901A *
Module Title : Human Genetics
Module Code : HS1003A*
Module Title : Molecular genetics of human disease: (biomed. sci. 4)
Module Code : HS1005A
Module Title : Human and Behavioural Genetics
Module Code : HS1104A*
Module Title : Human Disease Molecular Genetics
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£= have previously been module tutor
$ = run projects
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My main research interest is concerned with a common gene (GNB3) variant, present in half of all humans, known as c.825C>T. The GNB3 825T allele, predisposes carriers to hypertension, by as yet undefined mechanisms. I developed an interest in this research area through previous work with a single line of blind chickens with a retinopathy globe enlarged phenotype, which are severely mutated for the chicken equivalent of the human GNB3 gene. Recently a renal pathologist at Dundee University, Prof Stewart Fleming, identified that my GNB3 mutant, blind chickens, also consistently have extremely enlarged glomeruli and macrophage invasion, in their kidneys. This work would seem to indicate therefore that GNB3 may be predisposing humans to hypertension via its action in the kidney. With my former Honours student Jonnathan McGlinchey, I recently designed and patented a novel GNB3 genetic drug (patent number GB13055131.2), known as an antisense-morpholino, which appears to correct the pathogenic effects of the GNB3 825T cell line. This drug is likely therefore to have a therapeutic effect on millions of hypertension sufferers, who carry the 825T allele.
My other minor research area is in the use of Next generation sequencing methods to help identify the underlying pathogenic bases of patients suffering from hereditary forms of retinal degeneration. This method involves the sequencing of all of the patient’s genes in a day. The computer software base by base is then used to find the single letter change or changes in the DNA that are responsible for causing the patients disease. Using this method I successfully identified the underlying cause of a patient suffering from a rare form of cone-rod dystrophy. It is hoped that this method will be more routinely used for young patients who can then benefit from the new therapeutic methods of gene and stem cell therapy.
McGlinchey JC, Tummala H, Lester DH. Correction of the Pathogenic Alternative
Splicing, Caused by the Common GNB3 c.825C>T allele, Using a Novel, Antisense
Morpholino. Nucleic Acid Ther. 2016 Aug;26(4):257-65
Tummala H., Khalil HS, Islam MR, Sarah J. Jones SJ, Ellis IR, D’Ascanio I, Zhelev N, Lester DH The alternate GNB3 splice variant, Gβ3s, exhibits an altered signalling response to EGF stimulation, which leads to enhanced cell migration DOI: 10.7750/BioDiscovery.2013.9.3
Jamieson E, Lester D. The novel human p.I587V variant in the ZNF644 gene is
unlikely to be the pathogenic cause of dominantly inherited high myopia in a
Chinese patient. Invest Ophthalmol Vis Sci. 2012 Sep 28;53(10):6728
Tummala H, Fleming S, Hocking PM, Wehner D, Naseem Z, Ali M, Inglehearn CF,Zhelev N, Lester DH. The D153del mutation in GNB3 gene causes tissue specificsignalling patterns and an abnormal renal morphology in Rge chickens. PLoS One.2011;6(8):e21156.
Ali M, Hocking PM, McKibbin M, Finnegan S, Shires M, Poulter JA, Prescott K,Booth A, Raashid Y, Jafri H, Ruddle JB, Mackey DA, Jacobson SG, Toomes C, Lester DH, Burt DW, Curry WJ, Inglehearn CF. Mpdz null allele in an avian model of etinal degeneration and mutations in human leber congenital amaurosis andretinitis pigmentosa. Invest Ophthalmol Vis Sci. 2011 Sep 27;52(10):7432-40.
Tummala H, Ali M, Getty P, Hocking PM, Burt DW, Inglehearn CF, Lester DH. Mutation in the guanine nucleotide-binding protein beta-3 causes retinal degeneration and embryonic mortality in chickens. Invest Ophthalmol Vis Sci. 2006 Nov;47(11):4714-8.
Stewart AJ, Mukherjee J, Roberts SJ, Lester D, Farquharson C. Identification of a novel class of mammalian phosphoinositol-specific phospholipase C enzymes. Int J Mol Med. 2005 Jan;15(1):117-21.
Writer MJ, Marshall B, Pilkington-Miksa MA, Barker SE, Jacobsen M, Kritz A, Bell PC, Lester DH, Tabor AB, Hailes HC, Klein N, Hart SL. Targeted gene delivery to human airway epithelial cells with synthetic vectors incorporating novel targeting peptides selected by phage display. J Drug Target. 2004 May;12(4):185-93
Inglehearn CF, Morrice DR, Lester DH, Robertson GW, Mohamed MD, Simmons I, Downey LM, Thaung C, Bridges LR, Paton IR, Smith J, Petersen-Jones S, Hocking PM, Burt DW. Genetic, ophthalmic, morphometric and histopathological analysis of the Retinopathy Globe Enlarged (rge) chicken. Mol Vis. 2003 Jul 1;9:295-300.
Burt DW, Morrice DR, Lester DH, Robertson GW, Mohamed MD, Simmons I, Downey, LM, Thaung C, Bridges LR, Paton IR, Gentle M, Smith J, Hocking PM, Inglehearn CF. Analysis of the rdd locus in chicken: a model for human retinitis pigmentosa. Mol Vis. 2003 Apr 30;9:164-70.
Lester D, Farquharson C, Russell G, Houston B. Identification of a family of noncanonical ubiquitin-conjugating enzymes structurally related to yeast UBC6. Biochem Biophys Res Commun. 2000 Mar 16;269(2):474-80.
Jefferies D, Houston B, Lester D, Whitehead CC, Thorp BH, Botman M, Farquharson C. Expression patterns of chondrocyte genes cloned by differential display intibial dyschondroplasia. Biochim Biophys Acta. 2000 Jun 15;1501(2-3):180-8.
Farquharson C, Lester D, Seawright E, Jefferies D, Houston B. Microtubules are potential regulators of growth-plate chondrocyte differentiation and hypertrophy. Bone. 1999 Oct;25(4):405-12.
Lester DH, Farquharson C, Paton IR, Seawright E, Jefferies D, Whitehead CC, Burt DW, Houston B. A novel integral membrane protein is differentially expressed in the chick growth plate and maps to chromosome 1. Anim Genet. 1999 Aug;30(4):300-3.
Houston, B, Seawright, E., Jefferies, D., Hoogland, E., Lester, D., Whitehead, C., Farquharson, C. (1999) Identification and cloning of a novel phosphatase expressed at high levels in differentiating growth plate chondrocytes. Biochimica et Biophys Acta: Molecular Cell Research, 1448, 500-506.
Jefferies, D., Botman, M., Farquharson, C., Lester, D., Whitehead, C.C., Thorp, B.H. Houston, B. (1998) Cloning genes from chondrocytes using agarose gel differential display. Biochimica et Biophys Acta: Gene Structure and Expression 1396, 237-241.
Brown J., Dry K.L., Edgar A.E., Pryde F., Hardwick L.J., Lester D.H., Aldred M.A., Boyle S., Kaplan J., Ho M-F., Monaco A.M., Musarella M.A. and Wright A.F. (1996) Analysis of three deletion breakpoints in Xp21.1 and the localization of RP3. Genomics 37: 200-210
Lester D., Russell G., Barendse W. and Williams J. (1996) The use of denaturing gradient gel electrophoresis in mapping the bovine tumour necrosis gene locus. Mammalian Genome 7: 250-252.
Lester D. Brown J. Pryde F. Edgar S. Musarella M. and Wright A. (1996) The 6 megabase, X chromosomal, deletion breakpoint in a patient with DMD, CGD, Macleod phenotype and X-linked Retinitis pigmentosa involves an alu repeat. Genetical Research 68: 75
Usha A.P., Lester D.H. and Williams J.L. (1996) Excluding the mutations in the transmembrane region of FGFR3 as the cause of dwarfism in Dexter cattle. Genetical Research 68: 80
Urquart B.G.D., Lester D., and Williams J.L. (1996)Sequencing of a novel cDNA and mapping to bovine chromosome 7 by denaturing gradient gel electrophoresis. Anim. Genet. 27: 371-372
Teres V., Lester D.H., and Williams J.L. (1996) Mapping of Bovine Fibroblast Growth Factor Receptor 3 (FGFR3) to the telomeric region of chromosome 6, by SSCP analysis. Anim. Genet. 27:371
Lester D.H. (1995) BOOK REVIEW of: Two dimensional DNA typing. A parallel approach to genome analysis. By A.G Uitterlinden and J. Vijg (1994). Ellis Horwood, West Sussex UK. Animal Genetics 26, 61
Aldred M.A., Dry K.L., Knight-Jones E.B.,HardwickL.J., Teague P.W., Lester D.H., Brown J., et al. (1994) Genetic Analysis of a kindred with X-linked mental handicap and Retinitis Pigmentosa. Am. J. Hum. Genet. 55: 916-922
Lester D., Keen J., Inglehearn C. and Bhattacharya S.S (1992). Detection, by Hydrolink heteroduplex analysis, of a retinal binding site point mutation in rhodopsin, in a family with severe dominant retinitis pigmentosa. Genetical Research 59: 3: 234
Inglehearn C.F, Lester D.H., Bashir R., Atif U., Keen T.J., Sertedaki A., Lindsey J., Jay.M., Bird A.C., Farrar G.J., Humphries P. and Bhattacharrya S.S (1992) Recombination between rhodopsin and locus D3S47 (C17) in rhodopsin retinitis pigmentosa families. Am. J. Hum. Genet. 50: 590-597
Keen T.J., Inglehearn C.F, Lester D.H., Bashir R., Jay M., Bird A.C., Jay B., and Bhattacharrya S.S (1991) Autosomal dominant retinitis pigmentosa: Four new mutations in Rhodopsin, One of them in the Retinal attachment site. Genomics 11: 199-205
Keen J., Lester D.H., Inglehearn C.F., Curtis A., and Bhattacharya S.S (1991). Rapid detection of single base mismatches as heteroduplexes on Hydrolink gels. Trends Genet. 7:5.
Inglehearn C.F., Bashir R., Lester D.H., Jay M., Bird, A.C., Bhattacharya S.S. (1991) A three base pair deletion in the rhodopsin gene in a family with autosomal dominant retinitis pigmentosa. Am. J. Hum Genet. 48: 26-30
Lester D.H. and Wright A.F. (1991) Frequency of rhodopsin codon 23 mutation and retinitis pigmentosa. The Lancet 337:1609
Bhattacharya S., Lester D., Keen J., Bashir R., Lauffart B., Inglehearn C.F., Jay M., Bird A.C. (1991) Retinitis pigmentosa and mutations in rhodopsin. The Lancet 337: 185
Inglehearn C.F., Keen T.J., Lester D.H., Bashir R., Jay M., Bird A.C., Bhattacharya S.S. (1991) Rhodopsin mutations and phenotype in autosomal dominant
retinitis pigmentosa. Cytogenet. Cell Genet. 58: 1877
Aldred M.A., Jay M., Dry K., Lester D., Carothers, A.D., Bhattacharya S.S., Bird A.C., Jay B.S. and Wright A.F. (1991). Genetic localization of RP2 in 6 X-linked retinitis pigmentosa families. Cytogenet. Cell Genet. 58: 2053
Lester D.H., Inglehearn C.F., Bashir R., Ackford H., Esakowitz l., Jay M., Bird A.C., Wright A.F., Papiha S.S., Bhattacharya S.S. (1990) Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another:
Confirmation of genetic heterogeneity. Am. J. Hum.Genet. 47: 536-541.
Lester D.H., Bashir R., Jay M., Inglehearn C.F.,Bhattacharya S.S. (1990). Autosomal dominant retinitis pigmentosa: evidence for at least two genetic loci. J. Med. Genet. 27: 647
Inglehearn C.F., Jay M., Lester D.H., Bashir R., Jay, B., Bird A.C., Wright A.F., Evans H.J., Papiha S.S., Bhattacharya S.S. (1990) No evidence for linkage between late onset autosomal dominant retinitis pigmentosa and chromosome 3 locus D3S47 (C17): Evidence for genetic heterogeneity. Genomics 6: 168-173
Bellamy R., Inglehearn C., Lester D., Hardcastle A., Bhattacharya S. (1990) Better fingerprinting with PCR. Trends in Genetics. 6: 2: 32
Wadhwa R., Papiha S. Lester D., Ray V., Saha N., Bhattacharya S. (1989) X chromosome restriction fragment length polymorphisms in five racial groups: Rare variant detected with the RC8 (DXS9) probe in the Marthi population, India. Hum. Hered. 39: 309-312
Research: (1999) Named researcher on Wellcome Trust grant “Mapping and identification of the mutations underlying three forms of recessively inherited blindness in chickens”. Value of grant = £116,186 (shared with Leeds University and Roslin Institute)
(2003) Cystic Fibrosis Trust grant: Evaluation of siRNA-mediated inhibition of CFTR ubiquitylation to restore chloride ion channel activity in cells expressing DF508-CFTR CFT Project No: PJ 518 Value of grant = £12,500.00 (shared with UAD, Roslin Institute and Ninewells Hospital)