Studies of signaling domains in model and biological membranes through advanced imaging techniques: final report.

Cellular membranes have complex lipid and protein structures that are laterally organized for optimized molecular recognition and signal transduction processes. Knowledge of nanometer-scale lateral organization and its function is of great importance in the analysis of receptor-based signaling. In model membranes, we studied in detail the chemical and physical factors which result in lateral organization of lipids and lipid-mediated protein sequestration into signaling domains. In biological membranes, we mapped the location and follow the dynamic activity of specific membrane proteins involved in the immunological response of mast cells. These studies were enabled by our development of advanced imaging methods that provided both high spatial resolution and sensitivity to dynamical processes. Our technical approach was to combine the high sensitivity and time resolution of fluorescence imaging with the high lateral resolution of atomic force microscopy (AFM). Simultaneous fluorescence and AFM imaging allows correlation of the distribution and dynamic activity of specific biomolecules via fluorescence labeling with complete topographic information of the membrane. Overall, our unique imaging capabilities enabled us to examine membrane structure and function with much greater detail than was previously possible and thus provide a better understanding of cellular signaling

Pedagogy for Librarians

Most librarians are required to take classes on reference, collection development, and information organization in library school; courses on pedagogy, on the other hand, are usually optional, if they’re offered at all. This leads most librarians who end up with instruction duties to learn on the job. Activities and assessments can be learned on the fly fairly easily, but these often have little to no bearing on how much students actually absorb and recall weeks later because alone, they are usually insufficient to ensure deep learning. This chapter seeks to add the basics of pedagogy, a subject comprehensively covered in K-12 teacher preparation programs, to the librarian’s instructional repertoire

Integrated genomic and molecular characterization of cervical cancer.

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers

Integrated genomic and molecular characterization of cervical cancer.

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers