Junior Research Group Translational Control and Metabolism
Dr. Fabricio Loayza-Puch
Scheme of the differential ribosome codon reading (diricore)
approach
© dkfz.de
The demand for building blocks in cancer cells differs greatly from the one of a normal cell. In order to divide, a cell
must duplicate its protein content, a process that requires large amounts of energy and amino acid resources. To
cope with a higher demand of energy and building blocks, cancer cells rewire profoundly their metabolic networks.
However, the metabolic changes a tumor undergoes to adapt to deregulated growth might expose vulnerabilities
that can be exploited for therapy. To exploit amino acid vulnerabilities for cancer therapy, one must first identify
which amino acid is the most restrictive to the tumor. Our laboratory uses a combination of innovative genomics
tools, molecular biology, animal models, and bioinformatics to uncover these metabolic limitations in cancer.
Recently, we developed a novel approach to detect restrictive amino acids in cells and tumors. The rationale of our
approach is based on differential ribosome codon reading (diricore); we make use of ribosome profiling to detect
ribosomes stalled at specific codons. The accumulation of ribosomes at a particular codon indicates that the
corresponding aminoacylated tRNA might be limiting and suggests a deficiency of the amino acid. The diricore
approach can be used as a platform to sense these amino acid deficiencies in cells and tumors and to expose the
weaknesses of tumor's metabolic remodeling.
Future Outlook
RNA functions not only as a carrier of genetic information, but also as a catalyst and guide for the processing or
regulation of other RNA molecules. Using a combination of innovative sequencing techniques and functional genomics,
our group aims to understand the role of mRNA translation in cancer and metastasis. We explore the global impact of
RNA modifications and the role of non-coding RNAs on mRNA translation. At the same time, we use the global
positional information of ribosomes as a readout to infer metabolic deficiencies in tumors, such limitations have the
potential to be exploited as novel cancer therapies.
