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Dr C Toomes
Prof C Inglehearn
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
Prof Chris Inglehearn (Lead supervisor), Mr Martin McKibbin, Dr Manir Ali and Dr Carmel Toomes
Age-related macular degeneration (AMD) is the commonest cause of blindness in the western world, affecting approximately 3 million people in the UK alone. Visual impairment is caused when new leaky blood vessels grow inappropriately into the retina. Environmental factors play a role, with age and smoking having the greatest effects. However, the increased risk in relatives of patients and the results of twin studies all point to a strong genetic contribution. Genetics has implicated several genes in AMD, including those encoding HTRA1, several components of the complement system, Apolipoprotein E and the growth factor VEGF, which promotes the growth of new blood vessels, but more remain to be discovered. Recently an effective treatment has been developed using the drug Lucentis, an inhibitor of VEGF. However the treatment, though often successful, is expensive and does not work well in all patients.
Given our understanding of the genetic changes predisposing to AMD, we hypothesised that Lucentis therapy may be more effective in patients with some gene variants than with others. In a pilot study of 150 AMD patients we showed that this is indeed the case for one gene, HTRA1. This project will first aim to confirm our initial findings on a larger set of 400 AMD patients. It will also extend testing to include more gene changes known to be involved in AMD. If proven, this could save sight by allowing the targeting of treatment to those patients who could benefit most. Next the student will carry out a detailed examination of the gene with the biggest effect on treatment outcome, to track down the exact change involved and hence gain insight into the mechanism. Finally the student will use the same 400 AMD patients to test possible new AMD genes, including one we recently showed was defective in another eye disease very similar to AMD (Parry D et al 2009, Am J Hum Genet 84:683-91).
The PhD student will gain experience of a broad range of genetic techniques in the first phase of the project. Depending on initial findings, characterisation of functionally significant variant proteins will then lead to experience in molecular and cell biology techniques including cell culture, confocal microscopy, live cell imaging, transcript analysis, RT PCR and immunohistochemistry.
Age-related macular degeneration (AMD) is the commonest cause of blindness in the western world, affecting approximately 3 million people in the UK alone. Visual impairment is caused when new leaky blood vessels grow inappropriately into the retina. Environmental factors play a role, with age and smoking having the greatest effects. However, the increased risk in relatives of patients and the results of twin studies all point to a strong genetic contribution. Genetics has implicated several genes in AMD, including those encoding HTRA1, several components of the complement system, Apolipoprotein E and the growth factor VEGF, which promotes the growth of new blood vessels, but more remain to be discovered. Recently an effective treatment has been developed using the drug Lucentis, an inhibitor of VEGF. However the treatment, though often successful, is expensive and does not work well in all patients.
Given our understanding of the genetic changes predisposing to AMD, we hypothesised that Lucentis therapy may be more effective in patients with some gene variants than with others. In a pilot study of 150 AMD patients we showed that this is indeed the case for one gene, HTRA1. This project will first aim to confirm our initial findings on a larger set of 400 AMD patients. It will also extend testing to include more gene changes known to be involved in AMD. If proven, this could save sight by allowing the targeting of treatment to those patients who could benefit most. Next the student will carry out a detailed examination of the gene with the biggest effect on treatment outcome, to track down the exact change involved and hence gain insight into the mechanism. Finally the student will use the same 400 AMD patients to test possible new AMD genes, including one we recently showed was defective in another eye disease very similar to AMD (Parry D et al 2009, Am J Hum Genet 84:683-91).
The PhD student will gain experience of a broad range of genetic techniques in the first phase of the project. Depending on initial findings, characterisation of functionally significant variant proteins will then lead to experience in molecular and cell biology techniques including cell culture, confocal microscopy, live cell imaging, transcript analysis, RT PCR and immunohistochemistry.
Funding Notes
PhD project based in the section of Ophthalmology and Neuroscience (OPNE), Leeds Institute of Molecular Medicine (LIMM), University of Leeds.
Informal enquiries should be addressed to [Email Address Removed]. This project is available immediately to self-funded applicants with government scholarships or other sources of funding. Tuition and bench fees are payable for this project. Exceptional applicants may be nominated for Leeds University funded scholarships at the discretion of the supervisors.
Informal enquiries should be addressed to [Email Address Removed]. This project is available immediately to self-funded applicants with government scholarships or other sources of funding. Tuition and bench fees are payable for this project. Exceptional applicants may be nominated for Leeds University funded scholarships at the discretion of the supervisors.
Project supervisors
Career overview
Carmel Toomes obtained a BSc in Anatomical Sciences from the University of Manchester in 1994. In 1999, she completed her PhD at the University of Manchester under the supervision of Professor Mike Dixon, focusing on the Molecular Genetics of Blepharophimosis, Ptosis and Epicanthus Inversus Syndrome (BPES). Following her PhD, she held a post-doctoral position in Manchester under Professor Nalin Thakker, where she studied oral cancer and Papillon–Lefèvre syndrome. In 2000, Toomes moved to Leeds to take up another post-doctoral position with Professor Chris Inglehearn, investigating Optic Atrophy. In 2002, she became a Principal Investigator in the Leeds Vision Research Group after securing funding from the Wellcome Trust, followed by a Royal Society University Research Fellowship. After the conclusion of her fellowship in 2013, Toomes became a permanent member of the academic staff at Leeds.
Research interests
Associate Professor Carmel Toomes'' research is centred on molecular and cellular ophthalmology, with a particular emphasis on inherited diseases of the retina. Her specific areas of focus include Familial Exudative Vitreoretinopathy (FEVR), Foveal Hypoplasia, Leber Congenital Amaurosis, Optic Atrophy, Cone Rod Dystrophy, and Retinitis Pigmentosa. She is actively involved in several research consortia, including the European Retinal Disease Consortium, the UK Inherited Retinal Disease Consortium (UK IRDC), the Hearing and Sight GeCIP, the UK-EGG Steering Group, and the Medical Advisory Board for Retina UK.
Ophthalmic Research
Medical Genetics
Inherited Retinal Disease
Vascular Biology
Next-Generation Sequencing
Molecular Ophthalmology
Familial Exudative Vitreoretinopathy
Foveal Hypoplasia
Leber Congenital Amaurosis
Optic Atrophy
Cone Rod Dystrophy
Retinitis Pigmentosa
European Retinal Disease Consortium
UK Inherited Retinal Disease Consortium
Hearing and Sight GeCIP
UK-EGG Steering Group
Medical Advisory Board for Retina UK.
Career overview
Professor Chris F Inglehearn''s career in human genetics commenced with a Wellcome Trust Senior Basic Biomedical Fellowship at the Institute of Ophthalmology, UCL from 1992 to 1997. After five years, he transitioned to the School of Medicine at the University of Leeds, supported by a renewed Wellcome Fellowship, and was appointed Professor of Molecular Ophthalmology in February 2001. At Leeds, he established the Leeds Vision Research Group and later the Division of Molecular Medicine, which he currently heads. His research interests encompass diseases affecting vision, tooth development, and brain function. Professor Inglehearn''s research group employs genetics and genomics techniques, including next-generation and third-generation sequencing technologies, bioinformatics, cell and molecular biology, genome editing, and stem cell research, to elucidate the genetic and functional underpinnings of various inherited disorders. He collaborates extensively with national and international groups, being a leading member of the UK and European Retinal Disease consortia and part of the UK 100,000 genomes ''Eyes and ears'' Clinical Interpretation panel. From 2013 to 2017, he coordinated the EyeTN EU Initial Training Network, which supported 12 PhD students across seven European laboratories. To date, he has supervised 30 PhD students to successful completion and has authored or co-authored over 213 research papers on topics such as human inherited blindness, enamel defects, and brain disorders. His research outputs include significant contributions to the understanding of Mendelian diseases affecting the retina, such as retinitis pigmentosa and associated syndromes. He has also made strides in dental genetics, particularly in amelogenesis imperfecta, identifying numerous genes involved in this condition and establishing a comprehensive mutation database and diagnostic screening service in collaboration with the NHS. Additionally, he has engaged in psychosis research, exploring the genetic basis of schizophrenia in consanguineous populations. Professor Inglehearn holds a BSc in Biological Sciences from the University of Edinburgh (1984) and a PhD in Molecular Genetics from the same institution (1988). He has served on various professional boards and committees, contributing to the advancement of research in ophthalmology and genetics. In his educational role, he lectures and teaches medical undergraduates and MSc students on human inherited diseases and has extensive experience supervising PhD candidates.
Research interests
Professor Inglehearn''s research focuses on human genetics and vision research, particularly in the areas of inherited blindness, tooth and enamel development defects, and schizophrenia and intellectual disability. He leads the Leeds Vision Research Group, which investigates the genetic basis of Mendelian diseases affecting the retina, including retinitis pigmentosa, Cone-Rod Dystrophy, and Leber Congenital Amaurosis. The group employs genetics and genomics techniques, such as next-generation sequencing, bioinformatics, and genome editing, to identify genetic causes and explore therapeutic strategies for these conditions. Additionally, Professor Inglehearn''s work in the Leeds Dental Genetics Group examines inherited conditions related to dental development, particularly Amelogenesis Imperfecta, an incurable disorder caused by mutations in multiple genes. His research has led to the identification of 14 genes associated with this condition and the establishment of a comprehensive mutation database and diagnostic screening service. Professor Inglehearn is also involved in the Leeds Psychosis Research Group, which studies the genetic underpinnings of schizophrenia, particularly in consanguineous populations. This research includes epidemiological studies and genetic screening in collaboration with international partners. Overall, his work has resulted in over 213 research papers, contributing significantly to the understanding of inherited disorders affecting vision and dental health.
Molecular Ophthalmology
Human Genetics
Vision Research
Inherited Blindness
Tooth Development
Enamel Defects
Schizophrenia
Intellectual Disability
Genetic Disorders
Genome Editing
Stem Cell Research
Bioinformatics
Next Generation Sequencing
Retinal Disease
Mendelian Diseases
Amelogenesis Imperfecta
Psychosis Research
Epidemiological Studies
Genetic Screening
Therapeutic Strategies
Collaborative Research
PhD Supervision
Diagnostic Tests.
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