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.
- Compare progress in the
structure determination of the three types of cytoskeletal filaments.
Survey the roles these different filaments play in human disease.
- What causes a protein
to aggregate? Describe the protein components of proteostasis. Discuss
why proteostasis is important in human disease.
- 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.
- Evaluate our current
understanding of protein stability. Describe how our knowledge of
protein structures from thermophilic organisms have contributed to this
debate.
- 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.
- 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?
- 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.
- 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.
- 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.
- 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.
- 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.
- Discuss the structures
and functions of the circadian clock proteins from cyanobacteria. How
do the structures of these proteins determine their function?
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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/).
- 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.
- 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
- 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.
- 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.
- 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.
- Discuss
the
many
cellular processes that are regulated by a protein modification
involving ubiqutin.
- 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?
- 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.
- 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