Molecular Biology written projects 2012
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1 The Prokaryotic Cytoskeleton
Describe the homologs of mammalian cytoskeletal proteins found in prokaryotes and discuss
the role for the cytoskeleton in bacteria (JG)
2 Protein folding and molecular chaperones in archeabacteria.
Describe the array of molecular chaperones in these bacteria and discuss the issues for protein
folding in extremes of temperature. (JG)
3 Aging and protein damage in yeast.
Describe what happens to yeast proteins when cells age and discuss how yeast are still able to
produce ‘young’ daughter cells (JG)
4 The cytoskeleton as a target for anti-cancer therapeutics.
Explain why/how these dynamic structures are the targets for some anti-cancer therapeutics
and discuss the future directions of this field (JG)
5 The proteasome
Describe the structure and function of this protein oligomer and discuss its involvement in
human disease (JG)
6 Evolution of the eukaryotic chaperonin CCT
Discuss how/why the unique subunit composition of CCT may have evolved.(JG)
7 The prions of yeast and mammals
Describe the theory of how proteins can be infectious agents and explain why they cause
disease. (JG)
8 Structure and function of the actin severing and capping protein gelsolin
Describe how this multi-domain protein is able to influence the dynamic nature of the
microfilament network. (JG)
9 Intermediate filaments and disease
Describe the different families of intermediate filaments and explain how they are involved in
several human diseases (JG)
10 The tubulin protein family
New isoforms of tubulin have recently been described. Give an overview of the members of
the tubulin family in mammalian cells and describe their specific roles in cellular processes.
(JG)
11 Epithelial-Mesenchymal transition and cancer
The epithelial-mesenchymal transition is a highly conserved cellular program that allows
polarized, immotile epithelial cells to convert to motile mesenchymal cells. This important
process was initially recognized during several critical stages of embryonic development and
has more recently been implicated in promoting carcinoma invasion and metastasis. Discuss
and summarize the major signaling pathways that regulate the epithelial-mesenchymal
transitions during both development and tumor metastasis. How can this understanding be
used in treatment of cancer?
(MKJ)
12 Prolactins role in breast cancer
Prolactin, a polypeptide hormone mainly produced by the anterior pituitary, is best known for
its effects on the mammary glands, where it regulates glandular growth and development, as
well as milk production and secretion. The role of prolactin in mammary gland development
makes this hormone a candidate factor in the control of initiation and progression of breast
cancer. However, it remains controversial whether prolactin promotes tumor growth, or
suppresses invasiveness by upholding a differentiated state. Give a description about the
current understanding about prolactin’s role in breast cancer. Which is your opinion, does
prolactin promote or suppress tumor growth? Discuss how knowledge about prolactin can be
used to develop a new drug for cancer treatment? (JN)
13 Next- Generation DNA sequencing. (JN)
Discuss the development of the DNA sequencing technology. Which are the current trends
and future directions? Speculate about different applications in a five-years perspective. What
can be the ethical and social consequences?
14 The role of epigenetics in cancer (MKJ)
There is increasing evidence that epigenetic changes play a critical role in the development of
human cancer. Discuss the current understanding about epigenetic and cancer.
15) Stem Cells and cancer (JN)
Cancer Stem Cells (CST) are a subset of the bulk tumour responsible for initiating and
maintaining the disease. Give a description about the current understanding of stem cells in
cancer. Discuss how this can be used to develop CSC-specific therapies.
16 Metastasis (MKJ)
Invasion and metastasis are hallmarks of malignant tumor progression and the main cause of
death in cancer. Discuss the different stages of metastasis and different key molecules
involved in these processes.
17 The ”RNA world” (PS)
Today, only viruses have genomes consisting of RNA. However, there are speculations that
very early in evolution, our present “DNA world” was preceded by an “RNA world”, with
RNA molecules as a role both as storage medium for genetic information and as catalysts.
How credible is this hypothesis?
18 RNA interference (PS)
This recently uncovered phenomenon of RNAi has shown to contain a complex set of
interactions between microRNA, silencing RNAs, RNA processing proteins, and chromatin
proteins. RNAi seems to influence both epigenetic and translational control. RNAi is also an
important experimental tool.
What can be said about the key mechanisms of RNAi, and how widespread is this
phenomenon in nature?
19 Biological clocks (PS)
Many biological phenomena display periodicities with different frequency. The bestcharacterised are those linked to the 24h cycle. Recently, there are also indications of crosstalk between biological clocks and the mitotic cell cycle.
Give a description of the current understanding of the mechanisms underlying biological
clocks.
20 Oncogenic mutations and the cell cycle (PS)
Human tumours are characterised by several mutations in a set of genes, which by this
association has been named oncogenes and tumour suppressor genes. Many of these are
closely linked to cell cycle progression.
Can deregulation of cell cycle control alone explain the occurrence of cancer, or are other
events such as increased genome instability also necessary to happen in the same cell?
21 Mitochondrial inheritance (PS)
The human mitochondrial genome is, like those of all other eukaryotes, quite small. It encodes
only a minority of the proteins and RNAs required to maintain the basic functions of a
separate genetic entity (replication, transcription, and translation), plus a few other proteins
for specific mitochondrial functions (respiration). Most mitochondrial proteins are encoded by
nuclear genes. How come a separate mitochondrial genome is still maintained, with all
associated genetic functions, to encode so few proteins? Mitochondrial inheritance also has
other unique features: a) it is maternally transmitted, b) as a consequence of the oxidation
reactions in the electron transport chain, oxidative damage exposes mitochondrial DNA to a
higher mutation pressure than nuclear DNA.
How do these challenges and special conditions affect maintenance and transmission of the
mitochondrial genome?
22 Retroelements in metazoan genomes (PS)
Repetitive elements of many classes (e.g. Alu, L1) constitute a sizeable fraction of genomes
of higher organisms, e.g. vertebrates. Those named retroelements carry signatures of cycles of
transcription and reverse transcription – dispersal in the genome, loss of the 5’ portion of
transcribed sequences, polyA tracts. Their high copy number has been explained by an
equilibrium between their propagation and a weak pressure to eliminate them from genomes.
Recently, it has been realized that many retroelements are found in protein-coding sequences.
Can an argument be made that retroelements contribute to protein sequence variability in
higher eukaryotes?
23 Imprinting (PS)
Imprinted genes were defined as being expressed uniquely from the maternal or the paternal
allele in diploid organisms. The other allele is silenced by epigenetic mechanisms. In
mammals, only a small number of imprinted genes were thought to exist. Recent findings
indicate that the concept of imprinting could be considerably extended. A large number of
genes have an allele bias of expression, giving not complete silencing of one copy, but
moderate differences in expression levels between the two alleles. Discuss the biological
usefulness of genetic imprinting, and describe what is known about its mechanisms, giving at
least one example.
24 ABC transporters (PS)
This large class of membrane-bound transport proteins are collectively responsible for
pumping ions and small molecules into and out of the cell. They are essential for nutrient
uptake and cellular resistance to toxic compounds including xenobiotics. Mutations in ABC
transporters have been implicated in human disease and drug resistance. Describe the ABC
transporter family with respect to evolutionary divergence, structure, and substrate specificity.
25 Microtubule organising centers (PS)
Microtubule organising centers, MTOCs (depending on the organism, also known as
centrosomes or spindle pole bodies), organises the microtubular network. As a rule, they are
required for chromosome segregation in mitosis and meiosis. Unlike most cytoplasmic
structures, their number is under strict control, and duplication of MTOCs is coupled to the
cell division cycle. The molecular mechanisms underlying its duplication and how this is
limited to once per cell cycle are not fully understood. Discuss what is known about
regulation and mechanisms of MTOC duplication, and the consequences for a cell when this
control fails.
26 Nuclear architecture (PS)
There is growing evidence that chromosomes occupy specific domains within the nucleus,
and that the movements of each chromosome at each step in the mitotic or meiotic cell cycle
are largely reproducible. Moreover, highly localised nuclear centers for DNA repair,
transcription, and replication can be observed microscopically. Review recent advances in the
cell biology of the eukaryotic nucleus, and discuss their implications for function of the cell.
27 The nuclear pore complex dynamic (NS)
The nuclear pore complex is not a stationary structure. Specific components of the nuclear
pore are able to change their morphology and several nucleoporins (protein components of the
pore) are mobile.
28 The nuclear pore complex maintenance (NS)
New nuclear pore complexes (NPCs) are added during mitosis but many cells do not divide
for prolonged periods of time. What mechanisms ensure the functional integrity of the NPC in
these cells? How are components of the NPC repaired or renewed?
29 The nuclear pore complex evolution (NS)
Similarities between structures in the nuclear pore complex and those in coated vesicles
support the hypothesis for their common evolutionary origin and suggest the idea that the
gigantic nuclear pore structure has evolved through extensive motif and gene duplication.
30 The nuclear pore complex and regulation of nucleocytoplasmic transport (NS)
How the composition of the NPC is linked to transport regulation? Does change in the NPC
physical shape affect translocation of macromolecules through the pore?
31 The nuclear pore complex and regulation of mitosis in diving cells (NS)
The nuclear envelope and nuclear pore complexes (NPCs) lose their integrity during the
mitosis. However, there is increasing evidence that links some of the NPCs to the different
stages of mitosis.
32 The nucleocytoplasmic transport of mRNAs (NS)
In contrast to all proteins and many RNAs, mRNAS do not use the importin b family and
Ran-GTP gradient for their transport through the nuclear pore complex (NPC).
33 Regulated nucleocytoplasmic trafficking of viral gene products: A therapeutic target?
(NS)
Is blocking viral infection by inhibiting the nuclear transport of viral gene products real
possibility?
34 Nuclear transport of signal transduction proteins (NS)
The nuclear translocation of signal-transduction proteins is an essential step in the control of
gene expression by numerous extracellular signals.
35 Functions of imortin b family proteins beyond nuclear transport (NS)
Several observations have suggested that Kaps have additional roles in the cell that are not
related to nuclear transport. Is the mechanism by which Kaps function in transport and in
these different activities universally conserved?
36 Are all NPCs the same? (NS)
Evidence of compositional variation of the NPC challenges the dogma that all NPCs within
the same cell are identical. There are also examples of NPC proteins that exhibit tissue
specificity.
37 Impact of gene mutations on the degradation of the cyclin D (JPA)