The Futerman lab was established in November 1990 in what was then the Department of Membrane Research. The main focus of the lab at that time, and still is today, is to understand how sphingolipids function in cell physiology. Sphingolipids are critical components of cell membranes, and changes in their levels have been implicated in a number of human diseases, including the sphingolipid storage diseases such as Gaucher and Tay-Sachs diseases. Over the years, there have been two major goals of the lab, with the first being attempting to understand how sphingolipid synthesis is regulated, along with understanding how mutations in genes encoding for enzymes that degrade sphingolipids lead to human disease. In the 1990s, the focus was on understanding these aspects in cell culture models, and from ~2005, the focus shifted to animal models. More recently, the lab has undertaken a series of in silico (computational) modeling studies, and has suggested that membrane lipid bilayers, where sphingolipids reside, are finely tuned molecular assemblies.
Some selected key events in the history of the lab include:
- 1993, determining the intracellular site of ceramide synthesis
- 1999, demonstrating a role for altered calcium homeostasis in neuronal cell models of Gaucher disease
- 2001, identification of the first mammalian ceramide synthase, followed by discovery of the six mammalian ceramide synthase isoforms
- 2003, determination of the 3D structure of acid-beta-glucosidase, the defective enzyme in Gaucher disease
- 2010, generation of the first mouse model defective in one of the ceramide synthase genes (namely ceramide synthase 2), followed by detailed characterization of this mouse
- 2012, discovery of a role for neuroinflammation in neuronal forms of Gaucher disease
- 2021, suggestion that the fluid mosaic model of membrane structure should be replaced by the ‘fine-tuned model’ of membrane structure
- 2024, generation of a designed form of acid-beta-glucosidase that is effective in a gene therapy regime to reduce symptoms of neuronal forms of Gaucher disease in a mouse model.
While in the peak years of lab activity, up to 20 people worked in the lab, currently the lab is much smaller, with no more than 10 people. Two of the features of the lab have always been to ‘have fun’, that is, that science is not a job but rather a passion, and secondly, that lab members should be encouraged to think 'outside the box’. With the latter in mind, one of the main focuses of the lab at present is to test whether current neo-Darwinian mechanisms can explain the emergence of both sphingolipids and of the complex pathways that generate them. Although such discussion is normally considered taboo in biological circles, in-depth analysis of the minutiae of metabolic pathways, such as those of the sphingolipid biosynthetic pathway, raises challenges to current neo-Darwinian mechanisms that should not be shunned or ignored.
@ Thanks to Rotem Tedhar for the poster explaining how the Futerman lab works:
