Augustinus Galih

Name

Name: Augustinus Galih
Nationality: Indonesian

University of Geneva / Department of Biochemistry / Sciences II,
30 quai Ernest-Ansermet,
CH-1211 Geneva 4,
Switzerland

Contact details: augustinus.galih@unige.ch, +41 22 379-6463

Biosketch

Augustinus Galih obtained his bachelor degree in Biology in 2008 from Gadjah Mada University in Indonesia where he studied the bioactive compounds of a fruit, buah merah (Pandanus conoideus Lamk.). He then attended a master’s program in Biotechnology at the same university in 2009. In 2010, he withdrew from the program and moved to Utrecht University in the Netherlands to attend another master’s program in Molecular and Cellular Life Sciences.

During his master, he studied protein-lipid interactions using bifunctional lipid analogs in the lab of Joost Holthuis at Utrecht University. He continued studying the same topic in a high-throughput manner using a microfluidic-based liposome array in the lab of Anne-Claude Gavin at European Molecular Biology Laboratory (EMBL) Heidelberg in Germany. He received a Master of Science in 2012.

The studies have seeded his interest in sphingolipid biology and high-throughput, large-scale screenings. In 2013, he joined the lab of Howard Riezman at University of Geneva as a PhD student to investigate the molecular mechanisms by which deoxy-sphingoid bases cause cellular toxicity. The project involves a genome-wide screening for the molecular targets of the metabolites in the nematode Caenorhabditis elegans.

Besides his interest in life sciences, he is an astronomy enthusiast. He also likes communicating sciences to societies. He has a personal blog about life sciences presented in layman terms, called Molecularis Animus. He is currently also a contributor of Wikipedia articles. He likes spending his spare time watching documentaries on natural sciences, arts, politics, economics, and humanities.

Project title: Deciphering the roles of deoxy-sphingoid bases in Caenorhabditis elegans

Project summary: Sphingoid bases or long-chain bases are the defining structural unit of the sphingolipids. The bases are long-chain aliphatic amines, containing two or three hydroxyl groups, with various structural modifications. The bases are synthesized in the early steps of the de novo sphingolipid biosynthesis pathway. The first reaction in the pathway is the condensation of palmitoyl-coenzyme A with serine catalyzed by serine palmitoyltransferase (SPT), which leads to the formation of a sphingoid base, sphinganine. The base can then be modified further to generate more complex sphingolipids.

Different from sphingoid bases, deoxy-sphingoid bases lack a hydroxyl group at the first carbon atom. Deoxy-sphingoid bases are normally present at very low levels, and usually are not noticed as they are swamped out by the much larger amounts of other sphingolipids. The bases are generated due to the substrate promiscuity of SPT. Besides using serine as a substrate, SPT is also able to use alanine or glycine at low frequencies. The reactions lead to the formation of two deoxy-sphingoid bases, 1-deoxy-sphinganine and 1-deoxymethyl-sphinganine, respectively (Figure below).

Figure legend: The structures of sphingoid base (e.g. sphinganine) and deoxy-sphingoid bases (e.g. 1-deoxy-sphinganine and 1-deoxymethyl-sphinganine). The hydroxyl group that is lacking in deoxy-sphingoid bases is indicated in the red-dashed circle.

Our preliminary results suggested that increased levels of deoxy-sphingoid bases cause toxicity in the budding yeast. In the nematode C. elegans, the metabolites might accelerate cell death triggered by oxygen depletion. In addition, the metabolites are implicated in the maintenance of the intestine structure of the worm. In humans, heterozygous point mutations affecting one of SPT subunits are associated with Hereditary Sensory and Autonomic Neuropathy type IA (HSAN IA) and with increased levels of the metabolites, indicating that the metabolites are implicated in the manifestation of the disease. Nevertheless, the precise roles of the metabolites in cell physiology are not known.

The aim of the project is to unravel the molecular mechanisms by which deoxy-sphingoid bases cause cellular toxicity in C. elegans. To this end, we will introduce one of the HSAN IA-associated mutations to increase the levels of deoxy-sphingoid bases in C. elegans. Next, we will use the worm in a genome-wide RNAi screen for genes implicated in the molecular pathways that lead to cellular toxicity. The positive genes will be subjected to functional profiling to cluster genes that function in similar pathways, and the subcellular localization of the corresponding proteins will be determined. Finally, we will conduct functional assays to test the roles of the metabolites in the pathways.

Supervisors

Howard Riezman (Université de Geneve, Switzerland)
Maya Schuldiner (Weizmann Institute, Rehovot, Israel)

Biosketch 1st scientific supervisor:
Howard Riezman received a Bachelors of Arts degree (1975) from Washington University in Saint Louis where he began his research career working on the lac operon from E. coli. He then moved to the University of Wisconsin-Madison under the supervision of Wayne M. Becker where he completed his PhD in Botany (1980) working on the biogenesis of glyoxysomal enzymes. He crossed the Atlantic to work as a postdoctoral fellow (Jane Coffin Childs Fellow) with Gottfried (Jeff) Schatz as a mentor on the biogenesis of mitochondria at the Biozentrum of the University of Basel. In 1983 he started his independent laboratory at the ISREC in Lausanne initiating studies on the endocytic pathway in yeast. He moved back to the Biozentrum as Full Professor (1988) where he continued his work on endocytosis and began studying GPI-anchored protein biosynthesis and traffic. In 2002 he moved to the Biochemistry department of the University of Geneva. He continues working on membrane trafficking, but has changed the emphasis of his research to the understanding of the metabolism and function of membrane lipids.

Howard Riezman was elected member of EMBO in 1997 and has served as department chairman in both Basel and Geneva. He has served on the Research Council of the Swiss National Science Foundation (SNSF) for 8 years and is currently a member of the Foundation Council of the SNSF. His work has received generous funding from the SNSF since 1983, as well as from the HFSPO, EU and ESF. He has recently been awarded the directorship of a National Center for Competence in Research (NCCR) in Chemical Biology by the Federal Department of the Interior.