Molecular Protozoology

Summary

Lipids are the major components of biological membranes, fulfilling structural functions, energy storage and intra-and intercellular signaling. Comprise a large group of compounds including fatty acids, sphingolipids and sterols glycerolipids, among others. Our laboratory is focused, from different perspectives, to the study of biochemistry and molecular biology of lipid metabolism in different eukaryotic microorganisms (protists). This is carried out using bioinformatic approaches, molecular biology and genetics and a wide range of analytical methodologies for the study of lipid species (Gaseous and Liquid Chromatography coupled to Mass Spectrometry and GC/MS- -LC/MS-MS Chromatography thin layer, etc.).

Research Lines

Identification of drug targets in the lipid metabolism of trypanosomatids

Our group has depicted the fatty acid and sphingolipid metabolisms in trypanosomatids. These organisms are responsible of serious human and animal diseases such as Chagas disease, caused by Trypanosoma cruzi, sleeping sickness (T. brucei) and leishmaniasis (Leishmania spp.). By mean of genetic approaches and the design of specific inhibitors, we have identified that two enzymes of the pathway are essential for the parasites, the D9 and D12 desaturases. We continue analyzing the essentiality of other desaturases and elongases, and developing new drugs, more efficacious and with potential clinical use. A new line of research focuses on the enzymes involved in lipoic acid biosynthesis.

Sterol metabolism in ciliate protozoa

Another line of work focuses on the metabolism of sterols in the ciliates Tetrahymena thermophila and Paramecium tetraurelia. T. thermophila is able of taking up sterols from the media and modifying them by a series of desaturations and dealkylation. By using reverse genetic approaches such as feeding-RNA interference and knock out mutagenesis, we succeeded identifying the D5 and D6 desaturases and the dealkylating enzyme, which is the first one described in nature. The consequence of these reactions is the synthesis of pro-vitamin D, which is accumulated in the ciliate membrane. This has obvious biotechnological applications in the creation of functional foods of animal origin, with the dual benefit of reducing cholesterol and the concomitant enrichment in pro-vitamin D. We are also studying the synthesis of glycogen and triglycerides, which act as carbon and energy stores. We have determined that glycerol (a cheap by-product of the biodiesel industry) is a good carbon source for the ciliates, repressing the accumulation of glycogen, but stimulating the synthesis of triglycerides, which can be used in biodiesel production.

Selected Publications

  • A novel Tetrahymena thermophila sterol C-22 desaturase belongs to the Fatty Acid Hydroxylase/Desaturase superfamily (2022) Sanchez Granel ML, Siburu NG, Fricska A, Cida NG, Maldonado LL, Nudel CB, Uttaro AD, Nusblat AD. J. Biol. Chemistry. En prensa.
  • Functional characterization of the first lipoyl-relay pathway from a parasitic protozoon (2022) Scattolini A*, Lavatelli A*, Vacchina P, Lambruschi DA, Mansilla MC, Uttaro AD. Molecular Microbiology 117, 1352–1365.
  • Phagocytic and pinocytic uptake of cholesterol in Tetrahymena thermophila impact differently on gene regulation for sterol homeostasis (2021) Hernández J*, Gabrielli M*, Costa J, Uttaro AD. Scientific Reports 11, 9067.
  • Genome-wide Transcriptional Analysis of Tetrahymena thermophila Response to Exogenous Cholesterol (2020) Najle SR , Hernández J, Ocaña-Pallarés E, García Siburu N, Nusblat AD, Nudel CB, Slamovits CH, Uttaro AD J. Eukaryotic Microbiol. 67, 209–222.
  • Improved characterization of polyunsaturated fatty acids desaturases and elongases by coexpression in Saccharomyces cerevisiae with a protozoan acyl-CoA synthetase (2018) Tripodi KEJ, Berardi F, Uttaro AD. Eur J Lipid Sci Technol. 120(5) 1700474.
  • Lipoic acid metabolism in Trypanosoma cruzi as putative target for chemotherapy (2018) Vacchina P, Lambruschi DA, Uttaro AD. Exp Parasitol. 186, 17-23.
  • Sterols metabolism in the filasterean Capsaspora owczarzaki has features that resemble both fungi and animals (2016) Najle SR, Molina MC, Ruiz-Trillo I, Uttaro AD. Open Biol. 6, 160029.