Unleashing T Cells for Adoptive Immunotherapy
Presenter: Dr. Shannon Oda, Research Associate, Fred Hutchinson Cancer Research Center
Adoptive immunotherapy with T cells genetically modified to recognize tumors is rapidly becoming a promising and evolving treatment option. Antitumor activity, however, can be dampened by both limited co-stimulation and triggering of immunoregulatory checkpoints that attenuate T-cell responses. In this webinar, Dr. Shannon Oda, a research associate in the group of Dr. Phillip Greenberg (Fred Hutchinson Cancer Research Center), will talk about development of a CD200R-based immunomodulatory fusion protein (IFP) to improve anti-tumor T cell function and significantly enhance survival in a model of AML.
Rewritable Multi-event Analog Recording in Bacteria and Mammal Cells
Monday, June 11 at 1 pm EST and Wednesday, June 13 at 3 pm EST
Presenter: Dr. Weixin Tang, Fellow at the Jane Coffin Childs Memorial Fund for Medical Research
In this webinar, Dr. Tang talks about two CRISPR-mediated analog multi-event recording apparatus (CAMERA) systems that use base editors and Cas9 nucleases to record cellular events in bacteria and mammalian cells. The devices record signal amplitude as changes in the ratio of mutually exclusive DNA sequences or as single-base modifications. They achieved recording of multiple stimuli in bacteria or mammalian cells, including exposure to antibiotics, nutrients, viruses, light, and changes in Wnt signaling. Reliable readout required very few cells, and the order of stimuli can be recorded through an overlapping guide RNA design, and memories can be erased and re-recorded over multiple cycles. CAMERA systems serve as “cell data recorders” that write a history of endogenous or exogenous signaling events into permanent DNA sequence modifications in living cells.
Tools to Validate Conditionally Reprogrammed Tumor Cell Line Models
Tuesday, June 12 at 10 am and 4 pm EST
Presenter: Dr. Seema Agarwal, Georgetown University Medical Center, Center for Cell Reprogramming
Cell lines historically have been pivotal in advancing both basic and translational cancer research. For decades, scientists have attempted to develop bona fide models for growing and studying primary tumors outside of the human body. Even today, one of the greatest challenges in cancer biology research has been the development of a method to generate stable cancer cell lines from primary and metastatic tumors that can recapitulate the genotypic and phenotypic landscapes of the tumor of origin. Most primary cell cultures, regardless of the method used to generate them, suffer from limited lifespan due to a gradual decrease in proliferation rate eventually leading to cellular senescence. To address the current need of new models that can be robust, reliable and can keep the primary cells in culture for a long time without any genetic alterations, Schlegel’s group from Georgetown University described a method called “conditionally reprogramming” (CR) of cells. This CR technology uses mouse irradiated cells as feeder cells and ROCK inhibitor to grow patient’s epithelial cells from both normal and tumor tissue materials without any exogenous immortalization. However, before this rather novel CR cell model can be used for basic and translational research purposes it needed to be validated for genetic and phenotypic fidelity of the tumor of origin. This webinar is focused on the genomic tools that are being used to validate the CR technology for basic and translational research purposes.
Precision Genome Editing Using a CRISPR-mediated Base Editing Approach
Wednesday, June 13 at 10 am and 4 pm EST
Presenter: Dr. Pierre Billon, Postdoctoral Research Scientist, Columbia University Medical Center
Standard CRISPR-Cas9-mediated gene editing relies on Cas9-induced DNA double-strand breaks (DSBs). Recently, however, CRISPR-base editing has been developed to allow for the precise modification of targeted genomic bases without inducing DSBs. In this webinar, Dr. Pierre Billon, a research scientist at Columbia University Medical Center, will present a new strategy to efficiently inactivate genes by precisely converting four codons (CAA, CAG, CGA, and TGG) into STOP codons, which leads to gene disruption without DSB induction. A high frequency of these codons in a genome enables genome-wide disruption of genes in eukaryotic species and the precise modeling of over 32,000 cancer-associated nonsense mutations. Dr. Billon will also share his thoughts on the future development of improved base editors with increased precision and extended base type conversion and its impact on precision genome editing.d
Characterization of Mosquito Microbiome by Shotgun Sequencing
Thursday, June 14 at 10 am and 4 pm EST
Presenter: Dr. Jiannong Xu, Associate Professor, New Mexico State University
As a taxon proxy, bacterial 16S rDNA based profiling has been widely used for characterizing bacteriome in a metagenomic microbiota. The method is sensitive but limited to bacterial taxa and prone to PCR bias. It is inaccurate for quantifying the abundance of various taxa in a microbiota. Here, we introduce an NGS shotgun sequencing approach to characterize microbiota. The metagenomic shotgun reads can be de novo assembled into contigs and scaffolds for taxonomy and gene annotation. Since all the taxa in a sample are subject to sequencing, this approach is taxonomy unbiased. The taxonomic representation, although dependent on sequencing depth, is very close to the reality. Genetic capacity in a microbiota can be unraveled by gene function prediction based on metagenome contents. This webinar will feature examples of metagenomes from wild caught Aedes albopictus and Anopheles gambiae.
Testing a “Two Gene” Model for Sex Chromosome Evolution in Asparagus
Friday, June 15 at 10 am and 4 pm EST
Presenter: Alex Harkess, postdoctoral fellow with Dr. Blake Meyers at the Donald Danforth Plant Science Center
An elegant model for the conversion of an autosomal pair in a hermaphroditic species to a sex chromosome in a dioecious species was formalized by Deborah and Brian Charlesworth in 1978. Briefly, the conversion from autosome to sex chromosome could require just two loci linked perfectly in non-recombination on a Y chromosome: one locus must dominantly suppress female (pistil) organogenesis, while another locus must promote the formation of male (anther) organogenesis, but this model has never had strong genic support in any dioecious species. This can be tested using everyday garden asparagus, due to its evolutionarily young and cytologically homomorphic X and Y sex chromosomes. Using next generation sequencing techniques and Bionano optical maps, we identified a 1Mb region of non-recombination on the Y chromosome, but also found that a large part of this region did not exist on the X chromosome. In this webinar, Harkess will further discuss his findings and the implications for Charlesworth’s “two gene” model.
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