Hauptseminar 'Proteins and Disease' SS 2012

Type:            Seminar (2 SWS)
Ects:             4.0
Lecturer:      Burkhard Rost
Time:           Monday, 12:00 - 13:30
Room:          MI 01.09.034
Language:    English

 Content

 Topics related to the research interests of the group: protein sequence analysis, sequence based predictions, 
 protein structure prediction and analysis; interaction networks.

 Pre-meeting

Thursday, Feb 23rd, 14:30

The rules and hints for preparation of the seminar discussed given in the pre-meeting are also summarised in our Checklist.

 

Schedule

April 23   Lars von den Driesch: Structural Evolution of Enzymes
              Advisor: Andrea Schafferhans

April 30   Johannes Höffler: Integral membrane proteins and their classification
              Advisor: Edda Klopmann

May 7     Christiane Gasperi:Potassium channels
              Advisor: Edda Klopmann

May 14   Stefan Huber: Mutations in protein kinases and their role in human disease
             Advisor: Christian Schäfer

May 21   Kinga Balazs: The 1000 genomes project
             Advisor: Lothar Richter

June 4    Nikos Papadopoulos: HIV mutational pathways
              Advisor: Lothar Richter    

June 11  Andre Seitz: Physical and Genetic Interaction networks
             Advisor: Arthur Dong

June 18  Alexander Grün: The power of interaction networkds for associating genes with diseases
             Advisor: Tobias Hamp

June 25  Verena Friedl: Disease Networks
             Advisor: Arthur Dong

July 2    Paul Kerbs: Intrinsically Disordered Proteins in Human Diseases
             Advisor: Esmeralda Vicedo

July 9  Milot Mirdita: Use of GPUs for bioinformatics
            Advisor: Laszlo Kajan

July 16  Harold Tientcheu: Structural alignment and structure classification
            Advisor: Andrea Schafferhans

Topics

Structural alignment and structure classification

Dr. Andrea Schafferhans

Structure comparisons are the basis for many protein structure and function analyses. This seminar shall give an overview of structure comparison methods and explain the classification scheme behind SCOP/qCOPS.

Literature:

Structural evolution of enzymes

Dr. Andrea Schafferhans

The paradigm that "sequence determines structure and structure determines function" is central to the annotation of protein function. This seminar shall give an overview of studies that have analysed the relation between structural similarity and relatedness of enzyme function and the conclusions that have been reached with respect to evolution of new enzymes. It shall also review databases that can be used for such analyses.

Literature:

  • Rison,S.C.G. and Thornton,J.M. (2002) Pathway evolution, structurally speaking. Current Opinion in Structural Biology, 12, 374-382. www.ncbi.nlm.nih.gov/pubmed/12127458
  • Lee,D.A. et al. (2010) GeMMA: functional subfamily classification within superfamilies of predicted protein structural domains. Nucleic Acids Research, 38, 720-737. discovery.ucl.ac.uk/1299034/
  • Furnham,N. et al. (2011) FunTree: a resource for exploring the functional evolution of structurally defined enzyme superfamilies. Nucleic acids research, 44, 1-7. www.ncbi.nlm.nih.gov/pubmed/22006843
  • Please search additional related literature and follow references!

 


Integral membrane protein structures and their classification

Dr. Edda Kloppmann

The important class of integral membrane proteins (IMPs) provides the link between cell and environment or between different cell compartments and is for example involved in ion transport, signaling and cell adhesion. Structures of these proteins are particularly difficult to solve. Nevertheless, a significant number of structures is known today. This talk shall give an overview of IMP structure and how their orientation in the membrane can be determined from structure. A short introduction to the prediction of transmembrane segments from protein sequence shall be included.

Literature:

  • Lomize et al. (2006) Positioning of proteins in membranes: A computational approach. Protein Science 15: 1318-1333.
  • Tusnády et al. (2005) TMDET: web server for detecting transmembrane domains by using 3D structure of proteins. Bioinformatics 21: 1276-1277.

 

Potassium channels

Dr. Edda Kloppmann

Potassium channels form pores accross membranes selective for K+-ions. They constitute a major class of ion channels and occur in most organisms.

Literature:

  • Y Jiang, A Lee, J Chen, V Ruta, M Cadene, BT Chait & R MacKinnon. X-ray structure of a voltage-dependent K+ channel. Nature (2003) 423: 33–41.
  • ...

Mutations in protein kinases and their role in human disease

Dipl. Bioinf. Christian Schaefer

Protein kinases represent one of the largest protein families. Due to their role in a variety of biological processes, mutations play an important part in some human diseases. In this seminar, an overview of the protein family shall be presented. Furthermore, a selection of known genotype-phenotype relationships shall be discussed with the main focus on distinct features of disease-causing mutations.

Literature:

  • Lahiry P, Torkamani A, Schork NJ, Hegele RA. Kinase mutations in human disease: interpreting genotype-phenotype relationships. Nat Rev Genet. 2010 Jan;11(1):60-74.
  • Torkamani A, Schork NJ. Distribution analysis of nonsynonymous polymorphisms within the human kinase gene family. Genomics. 2007 Jul;90(1):49-58
  • ...

 

The power of protein interaction networks for associating genes with diseases

Tobias Hamp

Recent years have seen a large increase of known protein-protein interactions (PPIs) on the one hand and of known disease causing genes on the other hand. Computational biologists have combined these two types of data and now predict so far unknown disease genes with help of PPI networks. This seminar is supposed to give an introduction to current state-of-the-art methods.

Literature:

  • S. Navlakha and C. Kingsford. The power of protein interaction networks for associating genes with diseases.Bioinformatics (2010) 26(8): 1057–1063.
  • Vanunu O, Magger O, Ruppin E, Shlomi T, Sharan R, 2010 Associating Genes and Protein Complexes with Disease via Network Propagation. PLoS Comput Biol 6(1): e1000641.
  • Marc Vidal, Michael E. Cusick, Albert-László Barabási, Interactome Networks and Human Disease, Cell, 144(6): 986-998,

 

Alternative splicing and evolution

Tobias Hamp

Alternative splicing is universal and, as we recently learned, much more frequent than expected. This talk will give an introduction to what we know, remains to be discovered and how computational biology can come into play.

Literature:

  • I. I. Artamonova and M. S. Gelfand. Comparative Genomics and Evolution of Alternative Splicing: The Pessimists' Science. Chemical Reviews (2007) 107(8): 3407-3430.
  • H. Keren, L.-M. Galit and G. Ast. Alternative splicing and evolution: diversification, exon definition and function.Nature Reviews Genetics (2010) 11: 345-355.

Disease Networks

Dr. Arthur Dong

Molecular studies of diseases have traditionally focused on single genes (so called monogenic diseases). However, most common diseases are surprisingly complex, involving the interplay of multiple genes and proteins. The increasing availability of genome-scale data and the rise of systems biology ushered in a new era of network-based disease studies.

Literature:

  • The human disease network.PNAS 2007 May 22;104(21):8685-90

  • Network-based classification of breast cancer metastasis. Mol Syst Biol. 3:140 (2007)

Physical and Genetic Interaction Networks

Dr. Arthur Dong

Proteins are the main molecular actors in a cell, but they rarely carry out their functions alone. Instead, they physically interact with each other in most biological processes. The physical interactions can be either permanent, as in protein complexes, or transient, as in signal transduction. Proteins can also be highly correlated without interacting with each other physically; for example, one protein may induce or suppress another protein, or two proteins may participate in the same pathway. Such indirect interactions are termed genetic interactions. Both physical and genetic interactions in a cell form complex networks, with intriguing properties. In this study we combine the two types of networks to obtain further insights.

Literature:

  • Kelley, R. and Ideker, T. Systematic interpretation of genetic interactions using protein networks. Nature Biotechnology 23(5):561-566

Intrinsically Disordered Proteins in Human Diseases

Diplom. Biol. Esmeralda Vicedo

Intrinsically disordered proteins (IDPs) lack stable tertiary and/or secondary structures under physiological conditions in vitro.IDPs are involved in regulation, signaling, and control and their functions are tuned via alternative splicing and posttranslational modifications.Numerous IDPs are associated with human diseases, including cancer, cardiovascular disease, amyloidoses, neurodegenerative diseases, and diabetes. Overall, intriguing interconnections among intrinsic disorder, cell signaling, and human diseases suggest that protein conformational diseases may result not only from protein misfolding, but also from misidentification, missignaling, and unnatural or nonnative folding.

Literature:

  • Intrinsically Disordered Proteins in Human Diseases: Introducing the D2 Concept; Uversky VN, Oldfield CJ, Dunker AK.;Annu Rev Biophys. 2008;37:215-46.

  • Intrinsically disordered proteins from A to Z I; Uversky VN;The International Journal of Biochemistry & Cell Biology. 2011;43:1090-1103.

Protein design and engineering

Dr. Marc Offman

Proteins are central to most biological processes and their spectrum of functions is seemingly endless. Given that proteins are found in almost any living forms and each organism had to adapt to evolutionary pressure over million of years, a large number of different proteins have evolved. Some of these proteins could potentially be used as drugs, others need to be adapted (engineered), and for some purposes new proteins need to be designed. In protein engineering/design either known proteins are adapted in order to meet certain criteria such as increased stability, function, activity and recognition, or novel protein folds are created. Given the fact that proteins are large, complicated molecules with a huge number of degrees of freedom, protein engineering seems to be an unsolvable task. Nevertheless, methods are under constant development and show some success, as engineered proteins can already be used as therapeutics and as tools for cell biology.

Reference

Molecular Dynamics

Dr. Marc Offman