Absolute quantification of proteins from metabolic pathways

Biological pathways are regulated by various group proteins which act in a coordinated manner to alter the state of a cell or an organism. Previously, the pathway dynamics were understood by studying the gene expression of different proteins and correlating it to their abundances. As we are in the “Era of Pathway Quantification”, vast efforts are taken to understand the pathways quantitatively, but very little is explored on how absolute in vivo abundances of proteins can influence their dynamics.

To bridge this gap, we will investigate on how absolute molar abundances of proteins can impact cellular state using C. elegans and D. melanogaster as model systems.

Metabolic pathways in C. elegans

C. elegans are free living nematodes having  two distinct life cycles which are extensively controlled by metabolic rewiring. In one of the two cycles, they can enter a dormant state called “dauer” due to various environmental factors and exit only when the conditions are favourable. The energy expenditure during this state is kept at minimum, thus requiring a strong metabolic shift. This gives us an opportunity to probe deeper into how metabolism is regulated at the protein level and how the molar abundances of enzymes and corresponding metabolites correlate.

Collaborator: Sider Penkov, Teymuras Kurzchalia Group, MPI CBG 

Retinal development & Photo transduction in D. melanogaster

Drosophila melanogaster is another classical model organism used in developmental biology. The compound eye development & visual acuity in Drosophila involves interaction of different pathways. We developed mutant models of different crucial eye developmental proteins and will investigate how it affects molecular abundances of proteins.

Collaborator: Sarita Hebbar, Elisabeth Knust Group, MPI CBG 

Original publications

Damla Kaptan, Sider Penkov, Xingyu Zhang, Vamshidhar Gade, Bharath Kumar Raghuraman, Roberta Galli, Júlio L Sampaio, Robert Haase, Edmund Koch, Andrej Shevchenko, Vasily Zaburdaev, Teymuras V. Kurzchalia
Exogenous ethanol induces a metabolic switch that prolongs the survival of Caenorhabditis elegans dauer larva and enhances its resistance to desiccation.  Aging Cell, 19(10) Art. No. e13214 (2020) DOI 

Sider Penkov, Bharath Kumar Raghuraman, Cihan Erkut, Jana Oertel, Roberta Galli, Eduardo Jacobo Miranda Ackerman, Daniela Vorkel, Jean-Marc Verbavatz, Edmund Koch, Karim Fahmy, Andrej Shevchenko, Teymuras V. Kurzchalia
A metabolic switch regulates the transition between growth and diapause in C. elegans. BMC Biol, 18(1) Art. No. 31 (2020)  DOI 

Bharath Kumar Raghuraman, Sarita Hebbar, Mukesh Kumar, HongKee Moon, Ian Henry, Elisabeth Knust, Andrej Shevchenko
Absolute Quantification of Proteins in the Eye of Drosophila melanogaster. Proteomics, 20(23) Art. No. e1900049 (2020)  DOI 

Collaborations

Kurzchalia lab
Knust lab

Dr. Bharath Kumar Raghuraman

Contact: raghuram(at)mpi-cbg.de