Search..

Validating credentials, please wait...
Loading Events

« All Events

  • This event has passed.

The ESHG ‘National’ Fellowships

13 February

ESHG_2017_icon_square_256-7

The ESHG offers fellowships to young investigators under 35 years of age via the National Human Genetics Societies of Europe.

The national society will select one fellowship holder, which should comply with the following criteria:

  • She/he should be a member of the national society.
  • She/he should have shown excellence in the field of human genetics, and/or have given a good presentation/poster at the latest national meeting.

Limitations:

  • She/he should not be over 35 years of age
  • She/he cannot receive more than one fellowship in consecutive years.

Formalities:

Please, see the specific rules for participation of CSHG members here.

Benefits:

  • Free registration (including social events and lunches)
  • Accommodation and Travel support up to a maximum amount of EUR 600.-

Closing date for applications to the CSHG:

13th February 2017

 

Past Winners of the ESHG/CSHG Travel Awards

Year  2017
Photograph Petros Patsali, Winner of the 2017 National ESHG Conference Fellowship for Cyprus
Name and Title Petros Patsali, MSc
Affiliation King’s College London & The Cyprus Institute of Neurology and Genetics – Department of Molecular Genetics Thalassaemia
Abstract Title Less means more: knockdown of aberrant HBBIVSI-110(G>A) mRNA restores HBB expression and enhances gene therapy by gene addition in primary erythroid cells
Authors and Affiliations Petros Patsali, MSc1,2,*, Panayiota Papasavva, PhD1,3, Coralea Stephanou, MSc1,2,Soteroulla Christou, MD4, Maria Sitarou, MD4, Michael N Antoniou, PhD2, Carsten W Lederer, PhD1,3and Marina Kleanthous, PhD1,3

 

1Molecular Genetics of Thalassemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus, 2370; 2Department of Medical and Molecular Genetics, King’s College London, London, United Kingdom, SE1 9RT; 3Cyprus School of Molecular Medicine, 1683 Nicosia, Cyprus; 4Thalassaemia Centre, Ministry of Health, Cyprus; * Presenting Author (PetrosPa@cing.ac.cy)

 

Abstract Mutations reducing β-globin production and thus causing β-thalassemia are of global clinical importance. β-Thalassemia caused by the HBBIVSI-110(G>A) mutation (HGVS name: HBB:c.93-21G>A), which produces an abnormal splice acceptor site, is particularly frequent in many Western countries and causes severe thalassemia major in homozygotes.
Preclinical and clinical studies have highlighted patients with HBBIVSI-110(G>A) as difficult to treat with gene therapy by gene addition, suggesting an effect of the mutant locus on normal, endogenous or vector-encoded, β-globin alleles. Towards improved gene-addition treatment of affected patients and supposing that the mutant locus acts in trans by aberrant HBBIVSI-110(G>A)-derived mRNA, we therefore set out to reduce the latter by RNA interference. We recognised, first in a novel humanised murine erythroleukemia model and then in primary CD34+-derived erythroid cells from HBBIVSI-110(G>A)-homozygous patients, that specific knock-down of the aberrant HBBIIVSI-110(G>A) mRNA alone results in extremely significant induction of β-globin production from the mutant locus. In primary cells the resulting β-globin expression and phenotypic correction of erythroid-lineage differentiation is equal to or exceeds that achieved by same-sample control treatment with the clinically successful GLOBE gene-therapy vector. Furthermore, combination of HBBIVSI-110(G>A) knockdown with GLOBE results in significant improvement of both disease parameters compared to either treatment alone.
This study establishes aberrant HBBIVSI-110(G>A) mRNA as the main causative agent of disease severity in HBBIVSI-110(G>A) thalassaemia and as a potent target for mutation-specific gene therapy for β-thalassaemia. It moreover puts forward HBBIVSI-110(G>A) thalassaemia as a paradigm for the importance of allelic heterogeneity when applying gene therapy by gene addition.

 

Year  2016
Photograph  Maria_Loizidou_Photo
Name and Title Maria Loizidou, PhD
Affiliation  The Cyprus Institute of Neurology and Genetics – Department of Electron Microscopy and Molecular Pathology
Abstract Title <no abstract submitted>
Authors and Affiliations <no abstract submitted>
Abstract <no abstract submitted>

 

Year  2015
Photograph Petros_Smiles_20150515
Name and Title Petros Patsali, MSc
Affiliation King’s College London & The Cyprus Institute of Neurology and Genetics – Department of Molecular Genetics Thalassaemia
Abstract Title Towards gene correction of IVS1-110 β-thalassaemia
Authors and Affiliations Petros Patsali, MSc1,2, Claudio Mussolino, PhD3, Coralea Stephanou, MSc1,2, Michael N Antoniou, PhD2, Toni Cathomen, PhD3, Carsten W Lederer, PhD1,* and Marina Kleanthous, PhD1

 

1Molecular Genetics of Thalassemia Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus, 2370; 2Department of Medical and Molecular Genetics, King’s College London, London, United Kingdom, SE1 9RT; 3Institute for Cell and Gene Therapy, University Medical Center Freiburg, Freiburg, Germany, 79106; * Presenting Author (PetrosPa@cing.ac.cy)

 

Abstract Thalassemia is amongst the commonest single-gene disorders worldwide and caused by deficient production of α- or β-globin. The disease has limited curative treatment options, but as a monogenic disorder of the hematopoietic system is ostensibly an ideal target for gene therapy. Specific β-thalassemia mutations have already been addressed by the burgeoning field of genome editing, targeting mutations of minor prevalence in the West and combining homology-mediated gene repair with the expansion of corrected iPS cell clones

Our research is focused on the development of efficient gene-correction tools (TALENs and CRISPR-Cas9) specific for the common and severe HBBIVS1-110 (G>A) mutation, which in most Mediterranean and many Western countries has a frequency of above 20% (with 80% on the island of Cyprus) amongst β-thalassemia carriers. This mutation introduces an abnormal splice acceptor site in intron 1 of the β-globin gene, therefore retaining an intronic in-frame premature stop codon in the mature, aberrantly spliced mRNA.

In this study, we illustrate the high cleavage activity of novel IVS1-110-specific genome-editing tools (TALENs and CRISPR-Cas9) in HEK293T cells and in HBBIVS1-110-transgenic murine erythroleukemia cells. Towards the assessment of therapeutic efficiency of our designer nucleasese at the mRNA level, we have validated a multiplex RT-qPCR method for the absolute quantification of the correctly and aberrantly spliced HBB mRNAs. Finally, immunoblots indicate the partial correction of β-globin protein expression in treated HBBIVS1-110-transgenic MEL cells compared to mock controls. These preliminary data indicate HBBIVS1-110 as a suitable target for gene therapy genome editing and that our approach may serve as a model for the correction of many other intronic disease-causing mutations.

Details

Date:
13 February
Event Category:

Organizers

The European Society of Human Genetics
Cyprus Society of Human Genetics
Cyprus Ministry of Education