Informing treatment regimen design of immunotherapies for HIV

Elsje Pienaar

Immunomodulatory drugs could be part of a functional cure for Human Immunodeficiency Virus (HIV), but immunotherapies have so far proven ineffective. This is in part due to an incomplete understanding of the systems level host immune responses to immunotherapy. Non-human primate (NHP) data have shown that N-803, an interleukin-15 (IL-15) superagonist, can transiently reduce viral loads, but that efficacy wanes over time as more doses are given. This talk will describe our use of mathematical models of N-803 treatment in SIV-infected NHPs to estimate the contributions of three key mechanisms to treatment outcomes: 1) drug tolerance, 2) immune regulation and 3) viral escape. These models are then applied to inform treatment regimen design, advancing the potential impact of immunotherapy in HIV.

Mapping the uncharted genome at single-molecule resolution

Martin Smith

Less than 2% of the human genome codes for proteins, yet over 70% is transcribed into RNA. The great diversity of non-protein coding RNA transcripts (ncRNAs) and their roles in normal development and disease are confounded by our poor understanding of their biological functions. Given that over 80% of known genetic variants associated with human diseases ocurr outside of protein-coding regions of the genome, methods for the systematic annotation and classification of ncRNAs are essential to better understand the molecular protagonists of complex diseases. I will present how we are tackling this challenge using comparative genomics, machine learning and the latest single molecule sequencing technologies.

Daniel Reeves

Erica Moodie

Silent cancer agents: the ecology and evolution of oncoviruses

Carmen Lia Murall

Globally, 1 in 10 cancers is caused by a virus. Yet the vast majority of oncovirus infections do not progress to cancer or mortality. It is unclear, why these viruses, even with their potent oncogenes, are not more virulent. Under what conditions do they drive cancer? As we develop vaccines and treatments against oncoviruses, we create novel selective pressures and environments for which these oncoviruses can evolve. I will present my work into general oncovirus oncogenicity and I will discuss advancements in our understanding of the ecology and evolution of human papillomaviruses. Papillomaviruses are the best understood family of human oncoviruses and the global use of multi-strain vaccines against them is allowing us to study vaccine-driven evolution potential in human populations.

Martin Sauvageau

Caroline Colijn