esearch

Research News and Grants

CALL FOR RESARCH PROPOSALS INTO LOWE SYNDROME

Applications are invited for research funding from the Lowe Syndrome Trust.
The genetic basis for Lowe Syndrome is a defective gene OCRL1 that results in the deficiency of an enzyme Phosphatidylinositol 4,5-bisphosphate-5-phosphatase (OCRL1). Lowe’s oculocerebrorenal syndrome is a disorder affecting the brain, eyes, kidneys and bones. Research funds are available of up to £100,000 in the first instance, for funding a research studentship or assistant in understanding how the enzyme deficiency leads to observed phenotype.

Previous Lowe grant recipients are also invited to apply for a continuation grant.

For further information and Application Form please
Click here for the Grant Application form 

 
Contact: Lorraine Thomas, Lowe Syndrome Trust
Telephone 0207 794 8858

email: lowetrust@gmail.com

 

Closing date for applications TBA 2017


Proposals will be submitted to the charity medical advisory board and follows a peer review process. Previous Lowe grant recipients are also invited to apply for a continuation grant.  

The Charity is a listed non-commercial Partner of the National Institute for Health Research (NIHR). These are organisations that award research funds as a result of open competition across England with high quality peer review; fund research that is of clear value to the NHS; and take account of Department of Health and NHS priorities and needs in their research funding strategies. See 
www.nihr.ac.uk

The charity has funded and coordinated research projects across the UK, Europe and USA : 

 
Imperial College London
An inital grant award of £50,000 over 3 years was made to the Department of Chemistry, Imperial College  London to support a Phd studentship to research a chemical test for the OCRL enzyme. The research is entitled "Synthetic receptors for inositol phosphates: a novel diagnostic tool for the oculocerebrorenal syndrome of Lowe" by Dr Ramon Vilar-Compte and Dr Rudiger Woscholski . The grant will also be used to fund PhD student, Marianna Mirabelli, who recently completed a Masters degree in Biomolecular Sciences at the College. Research was continued in UK under Dr. Joachim Steinke and in Spain under Dr Ramon Vilar who  transferred to Tarragona  Spain at the Institut Catala d´Investigacio Quimica ICIQ). 

 University College London
An award of £50,000 over 3 years was announced to University College London "Assessment of Golgi structure and membrane traffic in cells lacking P1 (4,5) phosphatase OCRL1". 

 University of Dundee
A grant award was made to Dr John Lucocq of Dundee University for a 3 year research project entitled  "OCRL1 and its Lipid products - high resolution localisation and their role in membrane traffic and cell polarity".  See Grant Award

Manchester University
Dr Martin Lowe at Manchester University was initally awarded a grant for £50,000 for a 3 year research project entitled "Targeting of the phosphoinositide phosphatase OCRL1 to the golgi apparatus". A further grant of £72,000 was awarded for research entitled “Zebrafish as a model organism to study Lowe Syndrome” and featured in BBC news. The Zebra Fish is now available for further research.

Institute of Opthalmology
grant award was made to Moorfields Eye Hospital Institute of Ophthalmology to Dr T Levine for a research project into Lowe Cataracts entitled “Cell Biological Analysis OCRL1 in human lens epithelial cells.

Addenbrooke's Cambridge
A grant was awarded to Dr Antony Norden for a Kidney Cell research project at  the Department of Clinical Biochemistry, Addenbrooke's Hospital Cambridge.

Purdue University
A grant was awarded to Dr Claudio Aguilar for a project entitled “A Study of the behaviour of cells from patients suffering the Lowe Syndrome disease.  See 2013 Purdue research paper "The Lowe syndrome protein OCRL1 is involved in primary cilia assembly".

University of California, San Francisco
The charity awarded a grant of £100,000 to Professor Robert Nussbaum, who discovered the OCRL gene,  at the University of California. followed by a further grant of £61,000. Dr Nusbaum has developed a mouse model for Lowe Syndrome.

Great Ormond Street Children's Hospital
A grant of £9000 was made to support a Kidney Research Project at Gt Ormond Street Hospital/ICH London, headed by Dr Van't Hoff, Robert Unwin and Guido Laube, to whom Lowe Syndrome patients have donated urine samples so that OCRL kidney cells can be cultured and also made available for other research projects. The research is entitled “An investigation of intracellular metabolism in renal proximal tubular cells from patients with LOWE-Syndrome”.  A  paper was published in May 2008 Renal Phenotype in Lowe Syndrome. This concludes "Patients with Lowe syndrome do not have renal Fanconi syndrome but a selective proximal tubulopathy, variable in extent and dominated by low molecular weight proteinuria and hypercalciuria, the classical features of Dent disease"

History

The UK charity initially supported the USA Lowe Syndrome Assocation (LSA) with an award of $15,000 towards a total of $60,000 funding for two research projects. The first grant was to Prof. Jeremy W Thorner, Division of Biochemistry, Molecular Biology University of California, Berkeley, USA entitled "Phosphatidylinositol 4-Kinase, Pik1, Shuttles Between the Nucleus and the Cytosol Exploring the Physological function of PtdIns (4) Generation in the Nucleus".  The other research project entitled "Genetic Suppressors of 5-Phosphotase Mutants in C.Elegans" was carried out by Erik M.Jorgensen, Ph.D and Kimberley R. Schuske Ph.D in the department of Biology at the University of Utah in Salt Lake City USA. LSA reviewers commented on the projects as "well conceived and outstanding", "promising" and "have the potential to reveal significant insights about Lowe Syndrome and lead to new treatments".

 Clinical Research Workshop held at NIH USA in October 2002

The first international medical conference on Lowe Syndrome was held at the National Institutes of Health (NIH) in Bethesda, Maryland USA. in October 2002. The event was supported by a grant from the USA Office of Rare Diseases, the  Lowe Syndrome Association USA (LSA) and the Lowe Syndrome Trust. The Trust would especially  like to thank the LSA, lead by Kaye McSpadden, Director of medical affairs and Robert L. Nussbaun, M.D, head of the NHGRI and all the participants. The meeting was attended by about 30 people, with some parents and a specially invited group of distinguished doctors and researchers from across the USA, England, France and Italy from disciplines including opthalmology, neurology, nephrology, dermatology, dentistry and endocrinology. The purpose of the meeting was to discuss the clinical problems in Lowe Syndrome, consider issues relating to treatment and identify possible avenues for clinical research.  The UK Lowe Syndome Trust attendees were Dr David Taylor, Prof Bruce Caterson, Mike Harrison and parent Andrew Thomas.  

 The picture (courtesy of the LSA) shows some of the attendees: L-R front 2 rows: G.Jacobs, M.Tietz, Bruce Caterson (LST), Rebbeca Wappner, M. Tiez, David Walton, Christine Liang, Jean-Francois Gaddisseaux, Steven Wassner, Mario Loi, John Digiovanni, Graig Langman, Sharon Suchy, Richard Lewis. L-R back 2 rows: Robert Nissbaum, A Thomas (LST), Ann Smith, Andrea Gropman, Lawrence Charnas, Carol Clericuzio, Thomas Hart, David Taylor (LST), Mike Harrison (LST), Ingrid Taff, Eileen Brewer, Mark Benfield.  Missing from photo William Gahl, Steven Holland, Uta Lichter-Konecki, Leslie Whitty, Philip Zeitler.

The meeting addressed issues including the proper treatment of infantile glucoma and the advisabilty of lens implants, the link between renal disorders, cartilage and growth, growth hormone therapy, kidney  transplants, the nature of  cysts common in Lowe Syndrome and behavior observations (such as the hand-flapping well known to parents). Lowe Syndrome behavior was classified as an Autistic Spectrum Disorder. A full account of  the meeting is available from the LSA.       

On 2nd Dec 2004 a second symposium was held at the Royal Society in London which the UK researchers, European and others including R. Nussbaun, M.D, head of the NHGRI USA is attended. The outcome of the discussions on the links between Dents disease and Lowe syndrome clearly indicated that clinical syndromes as they are described in the medical literature are not simply accounted by a single or multiple gene defects. 

The meeting was chaired by Prof. Robert Unwin UCL and was opened by Lord Turnberg, Scientific Advisor to the AMRC, followed by Prof. Nussbaum head of the cell biology division of the National Human Genome Research Institute in the United States. Robert discovered the Lowe's syndrome gene on the X-chromosome and has been instrumental in Lowe Syndrome research. Presenters included Dr. William van’t Hoff, Great Ormond Street Hospital, Marianna Mirabelli from Imperial College London, UK and Spain, Dr. Martin Lowe from Manchester University, Prof. Chris Oliver from Birmingham University, Prof. Steve Scheinman, Upstate Medical University, USA and Dr. Pedro Cutillas from the Ludwig Institute. Nationalities at the meeting included France (ASL), UK, USA (LSA), Spain, Germany and Italy (AISLO).The results of a recent parent survey carried out by the LSA was offered to the participants. 

 On December 9th 2006, a group of researchers gathered in a satellite meeting at the 46th American Society of Cell Biology (ASCB) meeting in San Diego. This satellite meeting, sponsored by the Lowe syndrome Trust (UK) and given under the auspices of the largest and most prestigious professional scientific society for cell biology in the world, the ASCB, was well attended by 40-50 cell biologists, including a number of young investigators from outside the Lowe syndrome field who were attending the ASCB meeting.

A suggestion that had wide support was the establishment of a clinical data base of Lowe patients from around the world, to enable researchers to correlate clinical symptoms with DNA tests, Enzyme tests, and treatments.