Time : 1:30-4:30 pm , Jan. 22（Monday）
Venue: Room 300, SIBS Main Building, Yueyang Road 320
Host： Prof. Zefeng Wang
CAS-MPG Partner Institute for Computational Biology
1. Speaker: Rory Johnson , PhD
Assistant Professor,Department of Biomedical Research & Department of Medical Oncology University of Bern.
Towards complete annotation of long noncoding RNAs
Accurate annotations of genes and their transcripts is a foundation of genomics, but no annotation technique presently combines throughput and accuracy. As a result, current reference gene collections remain far from complete: many genes models are fragmentary, while thousands more remain uncatalogued—particularly for long noncoding RNAs (lncRNAs). To accelerate lncRNA annotation, the GENCODE consortium has developed RNA Capture Long Seq (CLS), combining targeted RNA capture with third generation long-read sequencing. CLS outperforms short-read assemblies in the depth and completeness of its annotations, yielding full-length lncRNA transcript models for the first time. I will discuss how GENCODE plans to use CLS to accelerate towards complete annotation of the non-coding transcriptome in human and mouse. I will then discuss how we utilize these annotations, in combination with CRISPR-Cas9 deletion and tumour mutation data, to comprehensively identify lncRNAs driving cancer.
My research aims to understand the role of long non-coding RNAs in disease, using a combination of bioinformatic and experimental tools. In 2007 I obtained my PhD, funded by the Wellcome Trust at the University of Leeds, applying genomic microarray and bioinformatic motif analysis to the regulation of microRNAs in neurodegeneration. Next, a postdoctoral position at the Genome Institute of Singapore exposed me to next generation sequencing and kindled my interest in little-known genes called long non-coding RNAs. This led me to the position of Staff Scientist with Roderic Guigo at the CRG, Barcelona, where I began work with GENCODE on lncRNA annotations. In 2016 I established the Genomics of Long Noncoding RNA in Disease (GOLD) Lab within the Medical Faculty at the University of Bern, funded by the NCCR “RNA and Disease” project. Currently our main interests are how to complete the human lncRNA annotation, and how to use CRISPR-Cas9 to find clinically-actionable lncRNAs in cancer and heart disease.
2. Speaker: Ralf Jauch , PhD
Group Leader, Guangzhou Institutes of Biomedicine and Health,CAS
Enhancing cellular reprogramming by directed factor evolution
To decode sequence-function relationship of transcription factor (TF) mediated cell fate conversions we use structural modeling and quantitative biochemical assays to analyze the formation of TF complexes on regulatory DNA in combination with genomics techniques. By contrasting the dynamic binding and gene regulation of paralogous TFs and engineered factors we begin to appreciate ‘enhancer codes’ directing cell fate programming. Further, we could identify functionally critical structural elements endowing selected TF to direct this process. We specifically ask how combinations of lineage specifying TFs (including SOX, OCT, PAX and FOX family proteins) work together to guide cell fate conversions in a step-wise manner. Lessons learned from these studies led us to hypothesize that native TFs are not optimized to direct artificial cell fate conversions and that they can be enhanced by directed evolution. To test this concept we generate TF libraries by randomizing selected amino acids and by recombining domains of paralogous genes. Using these libraries we perform pooled library screens, cell selection based on phenotypic read-outs and amplicon sequencing. This way, we identify artificially evolved TFs (eTFs) that program cell fates faster, more efficiently and in a more controlled fashion outperforming their wild-type counterparts. We propose that artificial reprogramming factor evolution presents a general paradigm that can be applied to any biomolecule-driven cell conversion system with utility in regenerative biomedicine.
Dr. Ralf Jauch studied Biology, Psychology and Archeology in Jena (Germany) and Manchester (UK) before doing his PhD in a molecular biology program from 2001-2005 at the Max-Planck-Institut für biophyskalische Chemie in Göttingen, Germany. In 2006 he got attracted to Singapore to join the recently established Genome Institute of Singapore (GIS, part of the A*STAR family) for postdoctoral training. From 2008-2013 he continued at the GIS as a research scientist and drove an interdisciplinary program at the interface of structural biochemistry, genomics and stem cell biology. In 2013 he joined the GIBH as principle investigator and carries out translation research within the DDP as well as academic projects within the stem cell institute.
All are welcome！