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Laccone Lab

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Franco Laccone, Assoc. Prof. Priv. Doz. Dr. med.

Facharzt für Humangenetik

Tel.: +43 (0)1 40160-56513
E-Mail: franco.laccone@meduniwien.ac.at

Research focus

The main research focus of Laccone Lab is the development and investigation of TAT (transactivator of transcription)- fusion proteins for neurodevelopmental and neurodegenerative disorders like RETT syndrome, Spinal Muscular Atrophy and Friedreich’s Ataxia. The technology requires the synthesis of the gene encoding for a fusion protein, linking the TAT transduction domain to the molecule of interest using a bacterial expression vector, followed by the purification of this fusion protein under either soluble or denaturing conditions. The purified fusion protein can be directly added to mammalian cell culture or injected in vivo into mice. Full-length TAT fusion proteins have been used to address a number of biological questions, relating to cell cycle progression, apoptosis, and cellular architecture.

The Laccone Lab is using methods such as Dynamic Light Scattering (DLS), Small Angle X-Ray Scattering (SAXS) and Nuclear Magnetic Resonance (NMR) spectroscopy to investigate protein stability (both conformational and otherwise), aggregation propensity and the presence of folded domains. Stable, non-aggregating protein constructs at optimal buffer conditions yield more favorable results in downstream assays, such as cell culture experiments

The application of a recombinant protein for a possible treatment of RETT syndrome has been patented: “Synthetic MECP2 sequence for protein substitution therapy“, (WO/2007/115578). However, we also attempt to develop and investigate recombinant proteins as a possible strategy for other genetic diseases.

Furthermore, Franco Laccone is interested in recruitment of patients with unknown illnesses for their identification.

Development of various TAT-fusion proteins for rare diseases like RETT syndrome, Spinal muscular atrophy and Friedreich’s ataxia

  • Expression, purification and structural characterization of MeCP2 constructs
  • Drug delivery across the blood-brain barrier for protein replacement therapeutic approaches against Rett syndrome
  • Changes of the blood-brain barrier during RETT syndrome
  • The role of MeCP2 in the interaction within the neurovascular unit

Generation of functionally active neurons using direct conversion from RETT patient fibroblast

Human fibroblasts from a MeCP2-deficient patient (and a healthy wildtype) are transfected with two episomal plasmids which encode for the transcription factors PAX6 and SOX2. Transfected cells are cultured in reprogramming medium for several weeks, resulting in induced neuronal progenitor cells (iNPs), which are in turn differentiated into neurons. This patient-derived cell model for RTT could serve as a promising tool for investigating phenotype rescue through the delivery of a recombinant MeCP2 protein.

Monoacylation of recombinant proteins for crossing the blood-brain barrier

A major challenge in correcting disorders like RETT syndrome is to induce BBB crossing of exogenously applied compounds.

Functional characterization of various candidate genes by CRISPR/Cas9 mediated genome editing

The CRISPR-cas9 system can be used to induce mutations that have previously been observed in patients. This allows the direct comparison of cells with a wildtype and mutant gene of interest isolated form other influences. CRISPR-cas9 makes use of a double strand break repair mechanism of mammalian cells, homology directed repair. There are only three crucial parts: (1) cas9, to induce a double strand break; (2) a site specific sgRNA or crRNA:tracrRNA complex that recruits cas9; and (3) a donor DNA harboring the desired mutation.

  • AIRETT – Associazione Italiana Rett (currently)
  • Elternhilfe für Kinder mit RETT Syndrome (from 2006 - 2016)
  • Austrian Institute of Technology
    Winfried Neuhaus, Priv.-Doz.
    Dipl.Ing. Dr., AIT
  • Center of Brain Research
    Sigismund Huck, Prof.
    Petra Scholze, Assoc.Prof., MedUni Vienna
  • Centre for Brain Research - the University of Auckland
    Bronwen Connor, Prof.

Current Lab Members

Franco Laccone, Assoc. Prof. Priv. Doz. Dr. med.

Group Leader

Phone: +43 (0)1 40160-56513
Fax: +43 (0)1 40160-956531
E-Mail: franco.laccone@meduniwien.ac.at

Medical University of Vienna
Center for Pathobiochemistry and Genetics                                               
Institute of Medical Genetics
Währinger Straße 10, 1090 Vienna

 

Hannes Steinkellner, Mag. Dr.

Lab Manager, Postdoc

Alexander Beribisky, PhD

Postdoc

Tel: +43 (0)1 40160-56547
E-Mail: alexander.beribisky@meduniwien.ac.at

Anna Huber, Mag.a

PhD Student

Phone: +43 (0)1 40160-56547
E-Mail: anna.b.huber@meduniwien.ac.at

Victoria Sarne, MSc

PhD Student

Tel: +43 (0)1 40160-56547
E-Mail: victoria.sarne@meduniwien.ac.at

Claudia Sulek, BSc

Master Student

Tel: +43 (0)1 40160-56547
E-Mail: -

Robert Beneke

Diploma Student

Tel: +43 (0)1 40160-56547

Former Members of Laccone Lab

  • Alexander Weiss (Master Student)

  • Sofia Geislberger (Bachelor Student)

  • Melanie Olczykowski (Master Student)

  • Mara Kluge (Diploma Student)

  • Philip Mausberg (Master Student)

  • Fabian Huber (Diploma Student)

  • Julia Etzler (Technician)

  • Katrin Rose (Master Student)

  • Neli Bounzina (Master Student)

  • Alexander Reitner (Master Student)

  • Zsofia Kormanyos (Master Student)

  • Azra Kurtovic (Master Student)

  • Anna Schönegger (Master Student)

  • Laura Gogoll (Diploma student)

  • Pinar Kehrer (Master Student)

  • Sandra Pferschy (Postdoc)

  • Gerwin Heller (Postdoc)