Back To Noticeboard Project Guidelines

List of Project Titles for PPS '13-'14


Note: Students are encouraged to describe and discuss the principles of their selected topic. It will be much more valuable to elaborate on the crucial ideas of the topic than to provide an exhaustive list of examples. Students who produce their own clear, relevant diagrams, using appropriate software, will be marked significantly higher than those who copy equally relevant diagrams from elsewhere with due acknowledgement.

  1. Compare progress in the structure determination of the three types of cytoskeletal filaments. Survey the roles these different filaments play in human disease.
  2. What causes a protein to aggregate? Describe the protein components of proteostasis. Discuss why proteostasis is important in human disease.
  3. Survey the range of protein structures that are found on the cell surface in prokaryotes and eukaryotes. Describe in detail the structure and function of one example from each kingdom that is important in human disease.
  4. Evaluate our current understanding of protein stability. Describe how our knowledge of protein structures from thermophilic organisms have contributed to this debate.
  5. Evaluate and compare the holdings of the protein domain databases Pfam, ProDom and SMART in terms of their coverage, ease of use, depth of coverage of each protein family, and the accuracy of the information provided.
  6. Survey the structures of proteins in the haemoglobin family still available in the PDB, from the earliest to the most recent. How have the more recent structures contributed to our understanding of the evolution and mechanism of action of these proteins, and of diseases such as sickle cell anaemia and the thalassemias?
  7. Discuss the biological role of the exosome complex and relate this to the structural details of the macromolecular cage utilized in the controlled degradation of RNA.
  8.  Describe and explain the algorithms used both in pairwise and in multiple alignments of protein sequences. How can the precision, accuracy and utility of such an alignment be evaluated? Describe a range of bioinformatics programs and techniques that rely on multiple alignments, focusing on the importance of the quality of that alignment for the validity of the result.
  9. Discuss the production of oxytocin from gene to active hormone. Include discussions of the structural information for the isolated hormone, the carrier protein neurophysin and bound complexes of the two as the gene product is processed biologically.
  10. Aminoacyl-tRNA synthetases must operate with a high fidelity. Justify this statement in terms of the structural differences found in a series of solved synthetases for different amino acids.
  11. Survey the structures of proteins that bind ATP. Discuss from a structural perspective the range of biological processes that use this type of protein recognition.
  12. Discuss the structures and functions of the circadian clock proteins from cyanobacteria. How do the structures of these proteins determine their function?
  13. Compare and contrast the current structural and biological knowledge for the small polypeptide hormones insulin and the insulin-like growth factors [IGFs]. Explain how these polypeptides feature in human disease.
  14. Using human genes and proteins as examples, describe the role of gene duplication in the evolution of protein structure and function. Your answer should include examples of single domain and multi-domain protein chains, protein monomers and oligomers and protein families.
  15. Lysozyme was one of the first proteins to have its structure determined. Describe and explain how studies of this protein have contributed to technical developments in structural and molecular biology, focusing particularly on X-ray crystallography and site-directed mutagenesis.
  16. Human serum albumin [HSA] acts as a key transporter for many small molecules in the blood stream including fatty acids and drugs and contains a number of bound metals. Survey the full range of protein structures currently found for HSA in the protein data bank and relate these to the known biological functions of the various binding sites located on the HSA protein structure. What post-translational modifications to HSA occur in a healthy and/or diseased individual.
  17. Cryoprotectants allow organisms to resist freezing and the formation of ice crystals if the temperature moves to below freezing. Survey the different structural solutions found by fish and insects to prevent damage due to extreme cooling.
  18. Ribonucleases are toxic to cells and were considered as a treatment for cancer. Survey this structural family and discuss how this damaging molecule is contained in the cell and why it proved not to be useful in cancer treatment.
  19. The PDBe contains a database of the symmetry of all deposited crystal structures which can be found from http://www.ebi.ac.uk/msd-srv/prot_int/pistart.html. Take some of the oligomeric states with unusual symmetries (less than 100 representatives), discuss the symmetries that arise and whether the unusual oligomeric state contributes to the function.
  20. Survey the structures of a wide range of proteins from the malaria parasite, Plasmodium falciparum. Which of these have been used as targets for anti-malarial drugs? Describe and explain using examples the properties that you would expect an ideal anti-malarial drug target to have.
  21. Survey the range of diseases that are caused by mutations in the ApoE gene and discuss some examples of the likely impact of the mutations on the encoded protein. Discuss the association of ApoE genotypes with risk for coronary heart disease. You may find it useful to register with The Human Gene Mutation Database (http://www.hgmd.org/).
  22. Starting from the Protein Knowledgebase (UniprotKB), describe the structural biology of human histone deacetylase 6 (HDAC6) and evaluate its roles in the nucleus and cytoplasm.
  23. Survey a range of membrane proteins with different structures submitted to the PDB in the last two years. Discuss the impact of these entries towards understanding human disease
  24. Key to the maintenance of higher life is the process of fixing atmospheric carbon. Discuss the structural features of the enzyme RUBISCO, its essential role in nature and how it is able to act as such a highly specific catalyst in plants.
  25. Mis-folding of proteins can result in many degenerative diseases of the brain of many species. Survey the role of prions in this class of disease and how the changes in native structure propagate the degeneration process.
  26. Select from http://proteopedia.org/wiki/index.php/Nobel_Prizes_for_3D_Molecular_Structure five or six cases where the Nobel Prize was given for the elucidation of a structure and consequent explanation of the function of one protein or protein family. Describe the structure and function of your chosen proteins and explain the contribution that its discovery made to structural biology more generally.
  27. Discuss the many cellular processes that are regulated by a protein modification involving ubiqutin.
  28. Describe in detail the structures of all proteins from the human immunodeficiency virus (HIV) that are available in the PDB. Explain the role that each plays in the virus life cycle and how it infects human cells. Which of these have been successfully targeted by drugs, and how do these drugs work?
  29. Kinase inhibitors are now some of the most important and widely used anti-cancer drugs, but their utility is often compromised by mutation in the kinase targets. Explain the molecular mechanisms for the development of this resistance in detail with reference to a range of structures of kinases bound to small molecules.
  30. Explain the development of the theory of the hydrophobic effect and its importance in protein folding throughout the twentieth century. How have structural studies of the network of water molecules close to protein crystal structures contributed to this? Refer to some recent high resolution structures in your explanation.


Please refer to the project guidelines before choosing your project.


Clare Sansom & Jim Pitts, June 2014