“Applied genomics to measure and treat renal allograft dysfunction”
Background:
To replace organs and tissues lost due to diseases or trauma, yearly millions of organ
transplantations are performed in Europe. Despite the tremendous impact of organ
transplantation, there is substantial room for improvement at the diagnostic and prognostic as
well as at the therapeutical level.
Since the introduction of kidney transplantation into medical practice, progress and optimism
have been abundant. Improvements in immunosuppressive drugs and ancillary care have led to
outstanding short-term (1−3-year) patient and renal allograft survival rates. This success is
mitigated by poor long-term (>5-year) graft survival rates, because of chronic rejection.
Currently available diagnostic and prognostic tools for patients receiving renal replacement
therapy are limited. It is very likely that genetic predisposition is one of the most relevant factors
predicting success/failure of kidney transplants. Gene expression profiling is a promising tool
that could be used in this field for early-stage diagnostics of chronic rejection, the prediction of
transplant survival (identifying “high-risk failures”) and success or optimal therapeutic
intervention.
Objective:
to perform a genome-wide expression profiling screen, using Illumina bead arrays or the novel
generation Solexa sequencing-by-synthesis technology (RNA-seq from Illumina), and identify
diagnostic and prognostic marker genes and novel therapeutical targets of chronic rejection in
patients with kidney transplants
Answer the following question:
Describe in detail the set-up for the experiment mentioned above, in which you indicate
patient groups, how many patients and which patient material, how in detail the gene
expression profiling experiment would look like and how you identify diagnostic and
prognostic marker genes and novel therapeutical targets of chronic rejection in patients
with kidney transplants.