Alberto Gatta

Name

Name: Alberto Gatta
Nationality: Italy

UCL Institute of Ophthalmology
Department of Cell Biology
11-43 Bath Street
EC1V 9EL 
London (UK)

Contact details:
a.gatta@ucl.ac.uk 
Tel: +44 (0)20 7608 4016
Skype: albgatta

Biosketch

Alberto studied Biotechnology in Milan where he obtained both his BSc and MSc Degrees. He dedicated the 18 months of his MSc thesis to study the feasibility and safety of a gene therapy approach to immuno-modulate the chronic-progressive phase of the Experimental Autoimmune Encephalomyelitis, an animal model of Multiple Sclerosis. During this internship in the lab of Gianvito Martino , under the supervision of Dr Roberto Furlan, Alberto acquired the broad range of laboratory skills required to work in the fields of neuroimmunology and chronic neuroinflammation: animal handling, neuropathology, primary cell culture, in vitro immunological assays, as well as molecular biology techniques to produce the third generation self-inactivating lentiviral vector in collaboration with Luigi Naldini Lab.

After this experience of research with high translational potential, he was called back by basic cell biology research: he’s currently using budding yeast cells in Tim Levine’s lab (at University College London) to study newly identified proteins involved in the general mechanisms of lipid traffic at membrane contact sites (and sphingolipid traffic in particular), and he’s convinced that understanding the regulation of lipid metabolism is of great medical importance for a broad range of human diseases.

Project title: Mechanism of sphingolipid traffic at membrane contact sites

Project summary:

The aim of this research project is to study mechanisms of sphingolipid traffic at membrane contact sites (MCS) so as to unveil important aspects of sphingolipid homeostasis.  Inter-organelle MCS are 10 nm-distant areas where heterologous membranes, usually the endoplasmic reticulum (ER) plus a partner organelle such as mitochondria, Golgi, endosomes, or the plasma membrane, come into apposition. The significance of these membrane contacts is yet to be fully described; however they are thought to play central roles in trafficking of lipids and calcium, and exchange of information.

This project focuses on the role of lipid transfer proteins (LTPs) at MCS in yeast cells, and it originated from preliminary data that yeast has a previously unrecognised family of LTPs. Each LTP domain is capable of solubilising a lipid, transferring it from one membrane to another. Initial characterisation places some of these proteins at ER-mitochondrial contacts and others at ER-plasma membrane contacts.

To verify this hypothesis, we want to describe yeast strains carrying single and double deletions of these genes: we will begin to define the LTP specificity by in vivo rescue with heterologous LTP domains; we will use tagged and radiolabelled lipids to study routes of lipid transport at MCSs; we will assay the ability of the LTP to transfer lipids in vitro from donor to acceptor liposomes; we will visualize endogenous ER-Golgi and ER-mitochondria contact sites using split YFP and SNAP/CLIP tag technology; we will analyse the role of these proteins on sphingolipid and sterol distribution; finally, we will crystalise LTP domains to identify the mechanism by which they bind lipids.

This work will be extended to analyse mutants in depth for defects in lipid metabolism. In collaboration with other partners of the Sphingonet, we will be able to study the genetic interactions (high-throughput images and genetic screens), the overall role in lipid metabolism (lipidomics study), and protein-protein interactions (proteomics).

Supervisors

Tim Levine (University College London, UK)
Kai Johnsson (EPFL, Lausanne, Switzerland)

Biosketch 1st scientific supervisor:

Tim Levine’s Lab main interest is the understanding and the regulation of lipid traffic across narrow cytoplasmic gaps (Membrane Contact Sites) where organelles come very close to each other. To address this issue, we approach the problem using the budding yeast Saccharomyces cerevisae model system, which is easily genetically tractable.

Among the key achievements of the lab, we identified and characterized the FFAT motif, its interaction with VAP (a conserved protein that links the endoplasmic reticulum to other organelles), and its use by lipid transfer proteins and key lipid regulators in accessing the ER; we investigated an earlier suggestion that phosphatidic acid regulates Opi1, a transcriptional regulator phospholipid metabolism, by demonstrating a direct interaction between this highly turned-over lipid in the ER and Opi1, which keeps Opi1 out of the nucleus, hence inactive; we analysed the role of VAP in yeast (called Scs2) in organizing the endoplasmic reticulum in yeast, showing that yVAP is required for the correct adhesion of ER to the cortex, without which cells cannot go through the cell cycle properly.