1. Introduction to Bioinformatics Research Project Most of the remainder of the semester will be devoted to a research project focused on phage genome analysis.

2. Introduction to Bioinformatics Research Project The project has both individual and group aspects. You can read more about it and learn about the different foci (even following the trajectory of two sample projects) by going to the Research Project topic page.

3. How to choose your research group The first important choice you need to make is the group you want to join, the research focus of you and about three of your colleagues.

4. How to choose your research group Below the inspirational message are links to group pages. Clicking on a link brings you to a login page. The User Name and Password are the same as given to you for the Who We Are site.

5. This page provides one or more review articles related to the general topic and links to reports on pertinent topics from previous years. Eventually, it will also provide a convenient means to contact your group members.

6. How to choose your research group I'll now give a very brief overview of the eight groups. It can't by itself give you much of an idea about the topic. It is designed only to make it slightly more comfortable for you to read the review article(s) on the topics' web pages.

7. How to choose your research group Lysogeny Phage Bacterial chromosome Phage genome Prophage Many phages must choose between two different fates upon infecting a host bacterium: Lysis or lysogeny. If lysogeny, then the phage integrates itself into the host's genome. If lysis, then the phage replicates and lyses (breaks open) the cell.

8. How to choose your research group Lysogeny Phage Bacterial chromosome Phage genome Prophage The Lysogeny Group will consider the proteins and DNA binding sites needed by phage to achieve and maintain the lysogenic state. (More on this next week!)

9. How to choose your research group The Lysis Group will consider the protein and DNA binding sites needed by phage to break the host cell. Killing your host is not a decision to be made lightly. Do it too soon and you kill yourself. Too late, and you lose the race. Lysogeny Phage Bacterial chromosome Phage genome Prophage

10. How to choose your research group The optimal time is when the the maximal number of phage particles have been manufactured. John Wertz, E. coli Genetic Stock Center, Yale U.

11. How to choose your research group John Wertz, E. coli Genetic Stock Center, Yale U. Ry Young (1992) Microbiol Rev 56:430-481 Then the phage synthesizes enzymes that break the host’s cell wall to cause local bursts. What are these enzymes in your phage? It’s up to you to find out and tell the world about it.

12. How to choose your research group The Sequence Bias Group will try to find measures of nonrandomness in the phage genomes. Here's one: different organisms have different preferences for the codons they use in protein synthesis…

13. How to choose your research group Do the phages have the same codon preferences as their hosts? Some phages carry their own tRNAs. Does this influence codon preferences?

14. How to choose your research group The most common gene on earth encodes a protein that copies the gene that encodes it and propagates copies of it. Wouldn’t you know it?

15. How to choose your research group The Mobile Element Group will attempt to identify such genes and the adjoining DNA sequences

16. How to choose your research group A bacterium typically needs to replicate its genome (say 3 million nucleotides) in a leisurely several hours, before the next cell division. Phages are often under much greater time pressure. For example, in the case of phage T4: 300 copies x 170,000 nt per copy = 51 million nt in 30 minutes! With higher DNA synthesis requirements than the host, many phage encode their own DNA synthesis proteins. Mueser TC et al (2010) Virol J 7:359

17. How to choose your research group But it’s not all protein. ALL phage DNA need a beginning point, an origin of replication, that determines where DNA synthesis will begin. The DNA Replication Group will look for both phage-encoded DNA synthesis proteins and origins of DNA replication on phage genomes. Mueser TC et al (2010) Virol J 7:359

18. How to choose your research group The Gene Regulation Group will look for proteins and protein-binding sites on phage genomes responsible for the regulation of the lytic process. We’ll soon study one such mechanism, regulating expression of the phage repressor. There are many many other strategies.

19. How to choose your research group In particular, the Gene Regulation Group may look for signals in the DNA responsible for the initiation and termination of transcription and translation.

20. How to choose your research group Genes are most often passed vertically, from parent to progeny. However there are cases where a gene is transferred horizontally, from one organism (or phage) to another, separately from the rest of the genome. The Phylogeny and Mosaicism Group will look for such genes and explore mechanisms for the phenomenon.

21. How to choose your research group Bacteria and their phages have been having at each other for a few billion years, and they've developed remarkable defenses and counter- defenses. The Phage-Host Antagonism Group will look for mechanisms phages have used to fight for survival.

22. How to choose your research group Enough easy generalities! Go and read the review articles and then submit your choices on the questionnaire posted on the calendar.