Andrei Lupas

Protein Evolution

Max Planck Insitute for Biology
Faculty in: TIPP, IMPRS


  • PhD in Molecular Biology at Princeton University,1985-91
  • Postdoctoral training at the Gene Center of the University of Munich and at the MPI for Biochemistry, Martinsried,1993-97
  • Senior Computational Biologist and Assistant Director of Bioinformatics at SmithKline Beecham Pharmaceuticals,1997-2001
  • Director at the MPI since 2001

Research Interest
Proteins are essential components of all living cells. It is thus hardly surprising that precursors of most proteins observed today existed at the time of the last common ancestor of all life. How did they evolve? Randomly synthesized polypeptide chains form folded structures in less than one in a billion cases, so it seems impossible that proteins arose by chance. We have proposed that folded proteins evolved by fusion and accretion from an ancestral set of peptides active as cofactors of RNA-dependent replication and catalysis. Using bioinformatics, we have reconstructed this "vocabulary" of ancient peptides and are now exploring experimentally the processes by which it could have led to the emergence of folded proteins, using methods in biochemistry and structural biology (crystallography, NMR, cryo-EM).
We also study how changes in protein structure create new functionality, both by attempting to functionalize newly created proteins in vitro and by exploring structure-function relationships in natural proteins. In the latter, our particular focus is on signal transduction across membranes and cellular mechanisms for protein quality control. An essential aspect of our work is the development of new bioinformatic tools, which we deploy in our MPI Bioinformatics Toolkit.

Available PhD projects

De novo Cytokine Design and Characterisation: Using computational design technologies, we aim to create novel proteins with therapeutic potential. In this project, we intend to further our previous work on the development of therapeutic cytokines with enhanced molecular and pharmacological properties. Particularly, the candidate will focus on the de novo design of cytokines that specifically target cells of predefined haematopoietic lineages, with the final aim of treating different types of haematopoietic disorders. The designed molecules will be characterized biophysically and their biological activity will be analysed by applying a wide spectrum of in vitro functional assays and in vivo animal experiments. This offers the doctoral candidate a great opportunity to work across disciplines in protein design, protein biochemistry, and clinical translational research.
The PhD student will work with Mohammad ElGamacy.

Applications are now closed.

Selected Reading

  • Zimmermann L, Stephens A, Nam SZ, Rau D, Kübler J, Lozajic M, Gabler F, Söding J, Lupas AN, Alva V. (2018) A Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core. J Mol Biol. 430:2237-43.
  • Afanasieva E, Chaudhuri I, Martin J, Hertle E, Ursinus A, Alva V, Hartmann MD, Lupas AN. (2020) Structural diversity of oligomeric β-propellers with different numbers of identical blades. Elife 8:e49853.
  • Fuchs AC, Ammelburg M, Martin J, Schmitz RA, Hartmann MD, Lupas AN. (2021) Archaeal Connectase is a specific and efficient protein ligase related to proteasome β subunits. PNAS 118(11).
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