The genome found in every cell of our body contains over 20 thousand genes and over 3 billion letters of DNA that sustains life, shapes who we are and determines our risks of having a disease. CRISPR/Cas (clustered regularly interspaced palindromic repeats) is a recently discovered antiviral defence system in bacteria that has become the favorite set of tools to edit and correct any diseased genome and change any sequence of DNA in precisely chosen genomic location performed not in a test tube but within the nucleus of our living cell.
Shipworms are marine bivalves that live and feed on wood. These bivalves, like most xylophagous and herbivorous animals, rely on bacterial symbionts to digest the recalcitrant lignocellulose component of plants. What’s unusual about shipworms is that bacterial symbionts are housed intracellularly in the specialized cells in the gills, therefore are not in direct contact with the ingested food particles.
Aberrant TGFβ signaling pathway may alter the expression of down-stream targets and promotes ovarian carcinogenesis. However, the mechanism of this impairment is not fully understood. By ChIP-chip and expression microarray, we have previously identified several SMAD4 targets in an immortalized ovarian surface epithelial cells. Bioinformatic analyses identified several SMAD transcriptional modules that predict expression changes after TGF-β activation. Knockdown of SMAD4 in CP70 ovarian cancer cells showed an increase in promoter methylation in some of those SMAD4 targets as demonstrated by sequencing-based analysis.
Metastasis claims 90% of all cancer-related deaths and remains clinically insuperable. The hallmarks of metastases are processes known as Epithelial to Mesenchymal Transition (EMT) and its reverse Mesenchymal to Epithelial Transition (MET) that enable primary carcinoma cells to migrate and start new tumors at distant organs. I will present an integrated theoretical and experimental approach that elucidates how cancer cells undergo EMT and MET, and how these transitions affect their ability to initiate new tumors.
Bioinformatics can play an important role in infectious disease surveillance and research from epidemiological data processing with geographic and temporal visualization to comparing genome phylogenies and structural modelling of mutations. As a classical example, interest in new influenza outbreaks as well as regular surveillance of circulating seasonal strains produce a constant flow of influenza genome sequences that need to be analysed and interpreted for epidemiological and phenotypic features.
Understanding the influences of molecular alterations on pharmacological responses in the omic sense is at the fore of the effort to make oncology treatments more effective and specific. At present, however, this remains a field in its infancy. The NCI-60 cancerous cell lines provide a premier set of databases and tools for systems molecular pharmacological studies.
Modern genomics research requires complex computational processing to integrate, analyze, and extract meaning from large, disparate datasets. While a multitude of commercial and open source bioinformatics applications are available, it is difficult to assemble a collection of tools that work together seamlessly to perform the required analysis. Even more difficult is performing analysis in a manner that documents the data, algorithms, and processing steps such that the results are easily published and reproducible.
Abstract – I will describe my work with the NCI TARGET Pediatric Acute Myeloid Leukemia consortium in which we are integrating data from 197 cancer whole genome sequences with mRNA and miRNA expression and DNA-methylation data, including verification of DNA variants via targeted re-sequencing, and frequency validation of confirmed variants in 650 additional patients.
One important aspect in the systems biology is to gain understanding in the systems level with molecular basis. With molecular basis in the model, new treatment or genetic perturbation can be designed in order to change the systems behavior. In this talk, I’ll focus on the methodology and an application for simulating a biological system, particularly for systems with noises.
All cells in our bodies encode the same genetic information yet different sets of genes are expressed in a given cell type to give it its particular identity. My laboratory studies how transcription factors (TFs) recognize genomic DNA to regulate when, where and to which level genes are expressed to direct cell fate decisions. We use structural modelling and quantitative biochemical assays to study TF dimerization on composite binding elements enriched in regulatory DNA sequences.