BIG 2021

CONCURRENT SESSIONS II

Thank you to all of the 2021 speakers and participants!

Click here to see members of the organizing committee for BIG 2021

“How are labs funded? Writing and reviewing grants in the Canadian context”

A large proportion of academic research relies on funding from government grants or charitable organizations. Most of this funding is awarded through a competitive grant application process conducted by peer review. In this workshop I will discuss my experiences in applying for and reviewing grants, scholarships and fellowships over the past two decades. I will identify common pitfalls and provide some general guidelines on structuring grant and fellowship proposals, how to interpret reviewer’s comments, and how to respond to rejection. There will be lots of time for discussion so bring your questions and experiences for the group.

"Gene-Environment Interactions in the Post-Genomic Era"

"Cancer genome landscapes shaped by prior therapy: Findings from the POG program"

Sequencing initiatives over the past decade have amassed a large amount of sequencing data and transformed our understanding of the genomic drivers of cancer. Many of these studies have focused on primary, treatment-naive disease. Advanced metastatic cancers are associated with reduced overall survival compared to primary disease and have often been exposed to multiple rounds of prior therapy for which they are resistant. By sequencing such tumours, we can gain insight into how prior therapy shapes the cancer genome and potential mechanisms of treatment resistance. The embedding of whole genome and transcriptome sequencing in the treatment planning of advanced cancer patients can inform treatment selection, and predict therapeutic response. Dr. Williamson will present findings from whole genome and transcriptome sequencing data generated as part of the Personalized OncoGenomics (POG) Program at BC Cancer, with a focus on the impact prior therapy has on shaping the genomic landscape and how sequencing can inform clinical decision making.

“Dissecting the interplay between histone marks & DNA methylation in the germline: insights into a sexually dimorphic epigenome”

Gene expression in mammals is regulated in part by DNA methylation. In recent years, a critical role for enzymes that add or remove covalent modifications from histone proteins has also been established. Intriguingly, mutations in the genes encoding such chromatin factors are causative for a number of related developmental disorders. For example, congenital mutations in DNMT3A, a DNA methyltransferase, are found in the overgrowth disorder Tatton-Brown-Rahman Syndrome, while mutations in the histone methyltransferase NSD1, which methylates histone H3 at lysine 36 (H3K36), are found in patients with a related overgrowth disorder, Sotos syndrome, who intriguingly have reduced DNA methylation, likely originating in the germline. While such clinical observations suggest an intimate crosstalk between these epigenetic marks, the role that H3K36 methylation plays in directing de novo DNAme in developing male and female germ cells was, until recently, poorly understood. I will discuss our efforts using genome-wide epigenomic and transcriptomic studies of genetic knock-out mice to dissect the roles of H3K36 methyltransferases in regulating DNA methylation and gene expression during gametogenesis, and the implications of our findings for development and disease.

“DIVERSITY LOST AND DIVERSITY REGAINED: THE PROMISE AND PERILS OF TAPPING CROP WILD RELATIVES FOR IMPROVEMENT”

Genetic diversity is indispensable for crop improvement.  However, most crops have undergone a domestication bottleneck and harbor less genetic diversity than their wild relatives.  Thus, there is considerable interest in reaching across the crop-wild boundary to re-acquire useful genetic variation that was lost during domestication and improvement.  Here I explore both positive and negative impacts of wild introgressions and discuss how the latter can be minimized, using cultivated sunflower (Helianthus annuus L) and its wild relatives as a case study.  Building on a data set of several reference sequences, numerous genetic maps, and > 2,400 re-sequenced genotypes, I show that around 10% of the cultivated sunflower genome is derived from introgressions with wild species.  These introgressions have introduced new disease resistance alleles into cultivated sunflowers, as well as components of the hybrid production system.  On the other hand, numerous chromosomal rearrangements differentiate cultivated sunflower and wild populations.  For example, a frequently employed wild donor species, H. petiolaris, differs from the cultivated sunflower by 6-8 translocations and 50-60 inversions, many of which are associated with important traits such as seed size and tolerance to low fertility soils.  These rearrangements hamper introgression from much of the genome and, if successfully introgressed into cultivars, can introduce genetic load and reduce recombination rates.  Gene presence/absence variation, which affects 27% of the genes in the cultivated sunflower pan genome, is also often associated with introgressions from wild species. While gene presence/absence variation appears to underlie key agronomic traits in cultivated sunflower, including disease resistance, fertility restoration, and flowering time, it also likely represents an important cause of linkage drag.  Such negative consequences of wild introgressions can be reduced by focusing pre-breeding efforts on a crop’s least divergent wild relatives, moving to a hybrid production system, which permits complementation of deleterious introgressions, or by deploying genetic engineering approaches (e.g., genome editing) to introduce foreign alleles, thereby eliminating the problem of linkage drag entirely.

"The Silent Genomes Project: Addressing the genomics divide faced by Indigenous Peoples in Canada. Focus on the Indigenous background variant library (IBVL)"

Genomic technologies are playing an increasing role in diagnosis and healthcare and hold the promise of ‘precision medicine’; however, Indigenous Peoples around the world do not have equitable access to these technologies and their downstream benefits. The Silent Genomes Project (SGP) aims to bridge this divide by increasing access to genomic technologies and improving diagnostic success for Indigenous Peoples with rare diseases in Canada. This is being accomplished through four separate but interconnected activities being carried out across the country (https://www.bcchr.ca/silent-genomes-project). Importantly, an Indigenous governance and capacity-building activity overarches the entire project, with multiple layers of Indigenous oversight informing all SGP activities.

The presentation will focus on one arm of the large Silent Genomes Project, the building of the Indigenous Background Variant Library (IBVL). A background variant library is a collection of DNA variants, which helps to determine variants that are common or rare. It is a tool used to rule-out the ‘noise’ of common variants in genetic analyses, to focus on the rare variants that are more likely to be disease-causing. However, the current background variant libraries, such as gnomAD, lack representation of Indigenous populations. To address this inequity, one initiative is to build an Indigenous Background Variant Library (IBVL). A joined overview will be presented, including the community engagement, the steering committee overviewing the governance and the technical implementation of the IBVL.