Student project 'Genetical Genomics: Stem Cell Biology in the Mouse'
Topic of research
We have previously shown that hematopoietic (i.e. blood forming) stem cells obained from various inbred strains of mice vary widely with respect to an array of functional properties. Specifically, stem cells from C57BL/6 and DBA/2 mice have been extensively studied; we have shown that DBA mice have a larger stem cells pool, that these cells have superior reconstitution kinetics, higher proliferation rates, deteriorate more rapidly during aging, and are more easily mobilized to the peripheral blood. In order to identify the genes underlying these traits we have mapped genomic loci associated with variation in various stem cell characteristics in BXD recombinant inbred mice. BXD mice have been derived by repeated brother-sister mating of parental C57BL/6 and DBA mice, during the course of which the genomes of both parental strains have recombined and have become fixed (i.e. homozygous) in a unique pattern in each individual BXD strain. The commercially available panel of 33 inbred BXD strains has been completely genotyped, and thus this panel forms an excellent tool to study phenotypes for which the DBA and C57BL/6 strain differ. We have recently performed an extensive study in which RNA samples were collected from highly purified hematopoietic stem cells isolated from the bone marrow of 22 BXD strains. These RNA samples were used to hybridize to Affymetrix gene array chips, containing ~12,000 transcripts. The map position of these transcripts is available. In parallel we have assessed the proliferative potential of each stem cell sample using in vitro stem cell assays. We will therefore be able to correlate the functional properties of each sample with the gene expression profile. This data set needs to be explored using statistical/linkage methods that partly have yet to be developed. The aims of this project are thus:
- detect gene expression patterns that correlate with specific stem cell characteristics,
- identify families of genes with differential expression patterns that segregate with specific genotypes,
- genetically map master-regulatory loci that influence the expression of entire gene families.
This project will not only be of significant relevance for the field of stem cell biology, but in addition will provide unique insight in the complexities of variation in gene expression, which is very likely to play an essential role in normal physiology.
The role of the student
The processing of these data consists of many steps, from image analysis up to interpretation of QTL patterns over multiple expression and phenotypic traits. The student is going assist in carefully collecting, modeling and analysing the data and interpreting the results. The student should take part and contribute actively in discussion groups on bioinformatic issues, and should present results of his/her work to other students and researchers in written (report) and oral form (seminar).
Required education/skills
You are a university student in one of the following disciplines: bioinformatics, statistics, computer science, mathematics, theoretical biology, quantitative genetics, physics, mathematics. You are expected to have an excellent academic record (list of examination marks from your university study) and be curious, creative and ambitious. You should be able to write scientific reports and be fluent in English language.
Additional Information and Application
For additional information and application, you can contact:
Prof.Dr. Ritsert C. Jansen, Groningen Bioinformatics Centre
Telephone number: +31-50-3633992 or +31-6-1246 1224
E-mail address: r.c.jansen rug.nl
AND/OR
Dr. Gerald de Haan, Department of Stem Cell Biology
Telephone number: +31-50-3632722
E-mail address: g.de.haan med.rug.nl
Or additional information can be obtained through one of the following links:
Reference
Jansen, R.C. and J.P. Nap (2001) Genetical genomics: the added value from segregation. Trends in Genetics 17: 388-391