174 - 2009 - Schedule

Kinetoplast DNA and RNA editing in trypanosomes

3-22-09 - April 21 (1) and April 30 (2) are still available!

 April 2

Presenters: Arthur Andakyan and Rogelio Pinon

Aphasizhev et al (2003). Isolation of a U-insertion/deletion editing complex from Leishmania tarentolae mitochondria. EMBO J. 22, 913-934 (PDF)

For those interested in looking at the two models of editing:

The correct model: Blum, B., Bakalara, N. and Simpson, L., "A model for RNA editing in kinetoplastid mitochondria: "Guide RNA" molecules transcribed from maxicircle DNA provide the edited information." Cell. 60, 189-198 (1990) (PDF)
The transesterification model (the beautiful but incorrect one!): Blum et al (1991) Cell 65, 443 "Chimeric gRNA mRNA molecules with oligo U tails covalently linked at sites of editing suggest that U addition occurs by transesterification PDF

April 7

Presenters: Andrew (not drinking the cane juice) Huang  and Jerry Van

Weng et al (2008). Guide RNA-binding complex from mitochondria of trypanosomatids. Mol. Cell 32: 198-209 (PDF)

Extra reading

Ochsenreiter T, Anderson S, Wood ZA, Hajduk SL. Alternative RNA editing produces a novel protein involved in mitochondrial DNA maintenance in trypanosomes. Mol. Cell Biol. (2008) 28:5595-604 (PDF)

Replication of kinetoplast DNA in  trypanosomes

April 9

Presenters: Vivian Lau and Sarah Samandary

Liu et al (2007). The rotational dynamics of kinetoplast DNA replication. Mol. Microbiol. (PDF)

Extra Reading

Kinetoplast DNA replication: Mechanistic differences between  Trypanosoma brucei and Crithidia fasciculata (PDF)

Here are some of my papers on the evolution of editing, for those who are interested in following up on our discussion:
Loss of gRNAs in the old lab strain of L. tarentolae
Review of evolution of RNA editing
Ancient origin of RNA editing
Evolution of RNA editing in tryps
Computer modeling of loss of kDNA minicircles

April 14

Presenters: Eric Peng and Aida Kolesnikova

Lindsay ME, Gluenz E, Gull K, Englund PT. A new function of Trypanosoma brucei mitochondrial topoisomerase II is to maintain kinetoplast DNA network topology. Mol. Microbiol. (2008) 70: 1465-76 (PDF)

For those interested in more reading:

Guilbride and Englund (1998) The replication mechanism of kinetoplast DNA networks in several trypanosomatid species. J. Cell Sci. 111, 675 (PDF) (a nice review of previous research).

Liu et al (2005) Fellowship of the rings: the replication of kinetoplast DNA. Trends in Parasitology 21: 363-9 (PDF)

Zhixing Zhao1, Megan E Lindsay1, Arnab Roy Chowdhury1, Derrick R Robinson2 and Paul T Englund (2008). p166, a link between the trypanosome mitochondrial DNA and flagellum, mediates genome segregation. EMBO J. 27: 143-154 (PDF)

April 16

Presenters: Marie Kim and Michelle Wray

Combe et al (2008). TREP, a novel protein necessary for gliding motility of the malaria sporozoite. Int. J. Parasitol. 39: 489 (PDF)

Extra Reading

Sultan et al. TRAP Is Necessary for Gliding Motility and Infectivity of Plasmodium Sporozoites (1997) Cell 90: 511-522 (PDF)

April 21

BLAST project due!

Presenters: Rachelle Levy and Harptreetpal Sandhu

Baum et al (2006). A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites. J. Biol. Chem. 24: 5197 (PDF)

Extra Reading

Alexander et al. (2005). Identification of the moving junction complex of Toxoplasma gondii: A collaboration between distinct secretory organelles. PLOS PAthogens, 1, 137 (PDF)

April 23

Presenters: Caroline Keegan and  Radu Dudas

Bjorn et al (2009). Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells. Science 323: 530 (PDF)

Extra Reading:

Carruthers and Boothroyd (2007). Pulling together: an integrated model of Toxoplasma cell invasion. Curr. Opinion in Microbiol. 10, 83-89 (pdf)

Morahan, Wang and Coppel (2009). No TRAP, no invasion. Trends in Parasitol. 25: 77 (PDF)

Maier et al (2008). Exported Proteins Required for Virulence and Rigidity of
Plasmodium falciparum-Infected Human Erythrocytes. Cell 134: 48-61 (PDF)

RNA interference: Mechanism and Biomedical uses

April 30 (Note that there is no meeting on April 28)

Presenters: Sarah Gustafson and Andrew Park

Okamura et al (2008). The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs. Nature 453: 803 (PDF)

Extra Reading

Ghildiyal et al (2008) Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 320: 1023 (PDF)

May 5 (last class) (Papers due for those not making a presentation or for Honors!)

Presenters: Mat Koo and Alex Funk

RNAi and Therapeutics

Song et al (2005). Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat. Biotech. 23, 709 (PDF)

Extra Reading:

RNA interference targeting Fas protects mice from fulminate hepatitis (PDF)

Wang et al. (2008). Therapeutic gene silencing delivered by a chemically modified siRNA against mutant SOD1 slows ALS progression (PDF)

Lopex-Frag et al (2008). RNA interference based therapeutics: New strategies to fight infectious diseases (PDF)

Liu et al (2008) Development of new RNAi therapeutics    (PDF)

Suggestions for presentations:

One person should give some background and go over any new techniques used. You could also present the techniques as the figure using them is discussed. Do not show the abstract first; I want the results to be presented inductively. Then both people should cover each figure in the paper, how the data is interpreted, and whether you think it is valid. At the end give some suggestions for further work. Try to ask questions of the audience (but know the answers!). I expect the audience to ask you questions also. I want this to be discussions rather than stand up seminars.  Either send me your Powerpoint file ahead of time or bring it on a flash stick. Format files for compatibility with Powerpoint 2003.

Suggestions for presenters: Do not just read from your PowerPoint slides. Use them as "talking points".

Ask questions of students (But be sure you know the answers!). Be enthusiastic!

Suggestions for students: Ask questions of presenter (you don't have to know the answers already!).

The grade will be based 50% on the paper or presentation and 50%  on participation in discussions.

Blast Project:

Click here for details and for link to L-complex sequences.

Try to turn in your projects by the April 23 class.