Martin Burg Grand Valley State Univ

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Genomics at Grand Valley State University

Course Overview:  The course (CMB 480: Drosophila Genomics) was first offered in W2010 semester, with 8 students in the class.  The class was divided so that finishing was done in the first half of the class and annotation the second half of the class.  The class met 7 hours each week, with 2-3 hr sessions and 1-1 hr session each week, with each section of the course (finishing and annotation) being covered in 7 weeks each.  The balance of the class has been changed due to alterations in what is being done in sequence improvement, with now about 2/3 of the class time spent on annoatation and 1/3 on sequence improvement projects.  This has allowed for the addition of curriculum in having students annotate not just the coding region of genes, but also the 5' UTRs, 3' UTRs, and TSS regions.  Students were responsible for finishing 1 fosmid and annotating 1 fosmid, using the assistance of thier computer partner.  Both oral and written reports were required of the students, for each of the 2 projects that they completed (or made progress on). 

In 2013 this course was accepted by the University Curriculum Committee and the Provost as a permanent elective course for the Cell and Molecular Biology major at Grand Valley State University.  In 2017 the course was reduced to 6 contact hours per week in the hope that more students would be able to fit it into thier schedule and a larger class wwas made available in the new Kindschi Hall of Science at GVSU.  There continues to be about 50% Juniors and 50% Seniors in the course.  Most participants have gone onto Graduate or Medical School.

Class numbers since the class was first taught can be seen in the sumary below in Implementation section.

Implementation

CMB 440: Drosophila Genomics Research winter 2017 semester, 6 hours each week, 11 students, 1 T.A.

CMB 440: Drosophila Genomics Research winter 2016 semester, 7 hours each week, 10 students, 1 T.A.

CMB 440: Drosophila Genomics Research winter 2015 semester, 7 hours each week, 9 students, 1 T.A.

CMB 440: Drosophila Genomics Research winter 2014 semester, 7 hours each week, 14 students, 2 T.A.

CMB 480 winter 2013 semester: 7 hours each week, 14 students, 2 T.A

CMB 480 winter 2012 semester: 7 hours each week, 10 students, 2 T.A

CMB 480 winter 2011 semester: 7 hours each week, 12 students, 2 T.A

CMB 480 winter 2010 semester: 14 weeks, 7 hours each week, 8 students, 1 T.A.

The class is divided into two main sections. In the first 2/3 of the course students now undertake ‘Genome annotation’ and each student is assigned an individual project from the GEP Project Management system. In the second half of the course, students will "improve the sequence" of 100,000 bp of DNA from a different Drosophila species, focusing mostly on mononucleotide runs and resolving or identfying gaps in the DNA sequence. Lecture and lab are interspersed with the actual implementation of the projects that students will be assigned taking a large amount of time each week. Computers are provided for the students' use in class, and are shared between 2 students. Students form groups of 2, which will be established and maintained throughout the course. Assignments are turned in by each individual, but can and may be worked on by the pair of students.  Reports (written and oral) are the main assesment tool used in evaluating students.

Lessons Learned and Future Plans

  1. Start lining up computers sooner than later.  Always check to make sure that if operating system changes, to test Consed or any other Unix-based application
  2. Asking (begging) for used computers is a quick and easy way to get the class started without large expenditures. 
  3. Link with the other 2 GEP members in the University so that we have a conitinuum of genomics experiences at the sophomore, junior, and senior levels. 
  4. When in doubt, call Chris and Wilson

Syllabus for CMB 440, Winter 2017

Time and Place: KHS 2270,T, TH, 3-5:50 PM
Instructor: Dr. Martin Burg
Office: 209 Henry Hall
E-mail: burgm@gvsu.edu
Office Hours: 9:30-11:30 AM Wednesday, 1:00-3:00 PM Friday, or by appointment
Student Course Assistants (1)

Pre-requisites
CMB 250, BIO 355, or BIO 375/376 are the pre-requisite courses for CMB 440.  It is expected that students in the course are upper level students that have an interest in applying their knowledge in genetics and cell/molecular biology to contribute to a genomics project that is the main focus of this class.

Course Overview
This research-based course provides junior and senior undergraduates the opportunity to work as a research team through a large-scale multi-center project, using support through the Genomics Education Partnership, and contribute to the overall project through sequence finishing and annotation of selected DNA contigs. The research problem involves ‘finishing’ or ‘improving’ the genomic DNA sequence from either the Muller F and Muller D elements of Drosophila biarmipes, Drosophila elegans, or Drosophila ficusphila.  In the second half of the semester, students will annotate the sequence of a DNA contig by comparing that species’ genomic region with that of D. melanogaster to discern patterns of genome organization, focusing on control regions from the Muller F and Muller D elements.  A more detailed view of the research problem will be reviewed in class as we get closer to each project.


Implementation
The class is organized into two main sections:

The class is organized into two main sections. In the first segment of the course students undertake ‘Sequence Improvement’ to improve the accuracy of ~80-100 kb of genomic DNA sequence from either the Muller F and Muller D elements of aDrosophila species, in collaboration with the Genomics Education Partnership.  The level of acceptable error after ‘sequence finishing’ is ~1/10,00 bases, about the level of error accepted by the mouse genome sequencing project.  In the second half of the course, students will annotate DNA sequence from a selected Drosophila species, leading to the annotation of Transcription Start Sites, or TSS regions and possibly other sequence motifs for other DNA binding proteins.  Lecture and lab will be interspersed with in-class implementation of the projects that students will be assigned.  Computers will be provided for the students for the first half of the course, and will be shared between groups of 2 students, which will be established and maintained throughout the course.  Because this is a laboratory course with lecture, make-up sessions are not possible.  If problems develop with attendance during the semester, it is the students’ responsibility to contact the instructor and determine ways that work can be made up.  Assignments should be turned in by each individual, but can and may be worked on by the pair of students.

Suggested Texts:
There are no required textbooks. Most of the lectures will be from research articles and handouts. All materials required for the course, announcements, reading assignments, etc. will be posted on Blackboard.
There are no required texts. The following books may be useful, depending on your background.

  • "Bioinformatics and Functional Genomics" by R. Pevsner, 2009 (2nd ed.), J. Wiley & Sons, NJ (recommended if you would like more introduction to the computer tools we use).
  • "BLAST" by I. Korf, M. Yandell, J. Bedell, 2003, O’Reilly ISBN_0596002998 (recommended for in-depth use of BLAST and interpretation of results).
  • "Genomes 3" by Terence A. Brown, 3rd ed, 2006, Garland Science ISBN_0815341385).

Some online resources that you will find useful:

Student Learning Objectives:
As a result of this course, students will be able to:

  • Use the analysis program Consed to assemble and evaluate DNA sequence data
  • Design oligonucleotide primers to generate new DNA sequence to improve the sequence of a fosmid
  • Report on the approach and steps taken in DNA sequence finishing a fosmid DNA clone
  • Use Repeat Masker in annotating DNA sequences
  • Use DNA data bases to compare sequence with in annotating sequence
  • Conduct various BLAST and FASTA searches for homology between nucleotide and protein databases
  • Use Genscan, Twinscan and other gene search tools to identify potential genes
  • Compare predicted genes and determine possible function using Clustal for comparative analysis
  • Report on the approach and steps taken in annotating a Fosmid DNA clone.

Lab Overview: Finishing

Either (1) video and/or demonstration, where noted below, or 2) having students perform hands-on, the following types of activities during the first half of the semester:

  • Direct sequencing techniques for plasmid DNA—both manual and automated (video)
  • QC procedures—how/when they are performed and why this is important
  • Looking at DNA sequence data—trace viewing and generating graphical representations of large data sets/comparative graphical views using Consed.
  • Finishing process—calling primers sequencing from fosmid or genomic DNA, adding additional data, making joins and editing, methods for assessing quality of finished sequence

Lab Overview: Annotation

Students will become familiar with commonly used DNA databases; model organism websites; genome browsers; RepeatMasker; Genscan and other gene prediction tools; BLAST, BLAT searches for similarity; CLUSTALW for comparative protein analysis. As time permits and the research dictates, other databases and comparative tools may be explored.  The focus of the laboratory will be to use the tools necessary to annotate the DNA contig assigned to each student.

Student Responsibilities

Students’ progress and learning will be assessed through the following means:

(1) Reports in oral and written format for both the finishing and annotation projects,

(2) Completing tutorial exercises and problem sets,

(3) Class-led discussions covering Figures from papers utilized in the course,

(4) Lab notebooks/records detailing the problems encountered in finishing and annotation and the strategies employed to complete the projects.

(5) Project files MUST be properly formatted and organized for submission or a 10% grading penalty will be assessed. 

(6) Any homework/project turned in late will be penalized at the rate of 10% per late class day (due dates will be placed on blackboard).

Grades will be assigned based on the following components:

  • Annotation report (paper and oral presentation) 35%                                                                                        -all files must be prepared properly prior to passing the course
  • Finishing report (paper and oral presentation)  35%                                                                                                                                                                                                        -project completion must have approval prior to end of semester
  • Problem sets, homework, quizzes: 15%
  • Participation in discussions of class readings 5%
  • Attendance/peer evaluations: 10%


Course Schedule
Week Topics
Activity
1
  Introduction to course
Introduction to the scientific question
Linux commands, Consed, and finishing
     Pre-course participant survey and quiz
GEP website navigating
Introduction to Consed tutorial
Graphical approach to consed tutorials
2
Issues concerning finishing/
sequencing chemistry/calling bases  
Sequencing center video
Simple fosmid /Complex fosmid tutorials
register students on database
Finishing Homework 1
3
adding reads/phred and phrap
Designing primers
finishing considerations
ordering primers
Begin finishing fosmid 1
Finishing homework due
        continue finishing fosmid 1/        start fosmid 2
4
adding reads/phred and phrap Designing primers,
finishing considerations;
ordering primers
      continue finishing fosmid 2/            begin fosmid 3  
5
Project checklist
Next generation sequencing
Review project report and oral presentation requirements
continue finishing fosmid 2/
fosmid 3 (if time permits)
6
Review problems encountered/discuss finishing project reports and presentations
Turn in finishing checklists and zipped file folder when fosmid is finished
continue finishing fosmid 3
7
Introduction to annotation
continue finishing projects/wrap up
8
Blast Basics, blast notes
Ab initio gene finding
run though example of D. virilis
Cleanup finishing projects
Begin sample annotation project review
Annotation tutorials
9
mRNA splicing, codons, and reading frames
building a gene model
Cleanup finishing projects
BLAST exercise 1 and 2 due 
10
Finishing presentations
(10 total, 5 each day)
Select and begin annotation projects
11
Class discussion concerning multiple isoforms
Rationale for accepting BLASTx results (which one to choose)
Written finishing reports due
12
Annotation discussions/
problem solving as a group
Initial gene models due for check
13
Annotation discussions/
problem solving as a group
Final gene models due for check
14
Annotation presentations (5 each day)
Written annotation reports due


Rubrics for the final projects in both finishing will be provided.
Due to the nature of the course, the schedule indicated in this syllabus may be adjusted based on the progression of the students and the projects.