- Jan Brugués
- Dye / Eaton
- Anne Grapin-Botton
- Stephan Grill
- Michael Hiller
- Alf Honigmann
- Meritxell Huch
- Wieland Huttner
- Anthony Hyman
- Florian Jug
- Elisabeth Knust
- Moritz Kreysing
- Carl Modes
- Gene Myers
- André Nadler
- Caren Norden
- Gaia Pigino
- Jonathan Rodenfels
- Ivo Sbalzarini
- Andrej Shevchenko
- Jacqueline Tabler
- Dora Tang
- Pavel Tomancak
- Agnes Toth-Petroczy
- Nadine Vastenhouw
- Christoph Zechner
- Marino Zerial
We are always looking for highly motivated and creative students (student interns, PhD students, post-doctoral researchers, visitors).
Project title: Mining the "dark proteome"
A single gene encodes multiple protein forms. It is estimated, that the human genome consists of ca. 20,000 genes, that codes for ca. 100,000 transcripts that generate >1,000,000 proteins. The mechanisms that increase proteome complexity include e.g. alternative splicing and post-translation modifications, that are used to regulate cellular homeostasis and response to stress. Additionally, an estimated 20% of the proteome in the living cell contains mutations due to the infidelity of transcription and translation. Sporadic examples show, that erroneous proteins can be beneficial and conserved via programmed errors in transcription and translation [2-4], similarly to alternative splicing.
The processes that generate diversity can be either regulated (programmed modifications and errors) or originate from the inherent noise in biological processes (stochastic modification or errors). We surmise that many more modification and errors exist yet to be uncovered, that we term collectively as “dark proteome”.
Our hypothesis is, that protein forms that initially originate from noise, can form a raw material of evolution and become the subject of natural selection.Examples show, that ribosomal frameshifting and STOP codon readthrough can become programmed when leading to novel function, and can ultimately become fixated at the genome level after gene duplication .
Mapping modifications and transcriptional/translational errors in proteomes is hindered by lack of a proteome-wide experimental methodology. The two main challenges are that these protein forms are 1) rare, 2) transient. Here, we aim at quantifying and mining the dark proteome by developing a dedicated experimental and computational mass spectrometry pipeline.Currently, MS/MS based proteomics experiments discard 50% of collected spectra, that do not map to canonical protein forms (hence they consist the dark proteome). However, recent success in systematic detection and quantification of errors in entire E.coliproteome gives us confidence, that a successful and powerful experimental and computational pipeline is possible in house at MPI-CBG/CSBD.
1. Penno, C., et al., Productive mRNA stem loop-mediated transcriptional slippage: Crucial features in common with intrinsic terminators.Proc Natl Acad Sci U S A, 2015. 112(16): p. E1984-93.
2. Dinman, J.D., Control of gene expression by translational recoding.Adv Protein Chem Struct Biol, 2012. 86: p. 129-49.
3. Matsufuji, S., et al., Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme. Cell, 1995. 80(1): p. 51-60.
4. Ketteler, R., On programmed ribosomal frameshifting: the alternative proteomes.Front Genet, 2012. 3: p. 242
5. Yanagida, H., et al., The Evolutionary Potential of Phenotypic Mutations.PLoS Genet, 2015. 11(8): p. e1005445.
Qualifications: Computational Biology, Chemistry
Advantage: experience with mass spectrometry
Students interested in a PhD project in the Toth-Petroczy lab are encouraged to apply to the International Max Planck Research School for Cell, Developmental and Systems Biology (IMPRS-CellDevoSys). Please check the list of recruiting group leaders for information on who is offering a PhD position and the deadline for application.
We are also supporting fellowship applications of outstanding postdoctoral researchers who wish to join our lab. This may either be through third party funding (Humboldt foundation, EMBO, DAAD, etc.) or through an ELBE postdoc fellowship by the Max Planck Center for Systems Biology Dresden (CSBD).