PhD Projects » ESR 15: Elucidating the role of the host cell during long-term in vitro HIV-1 evolution

Ali Movasati

My name is Ali and I come from Iran. After finishing my Bachelor’s degree at Tehran University in Biotechnology, I moved to Utrecht, the Netherlands, in order to study a Master’s program in Life Sciences. As I was coming from a mathematical background I felt motivated to do a minor in Bioinformatics during my Master’s as well. After realizing the power of big biological data in decoding the challenging biological questions, I decided to stay in this field and continue using bioinformatics tools and methods to explore the molecular and cellular landscape of life for the rest of my career. Right after my Master’s, I started working as a genomics data analyst at University Medical Center (UMC) Utrecht for 1.5 year, through which we compared the genomic landscape of primary and metastatic cancers using a large data set of WGS data.

Now I am absolutely excited to become part of the VIROINF community and take on a very intriguing and challenging PhD project in Dr. Metzner’s group at University Hospital Zurich. In this project I will use different types of high-throughput sequencing data from a long-term experimental evolution study of HIV-1 to fully characterize the evolution of HIV-1 and the factors that have been shown to influence its evolutionary paths, such as random processes, environment, and genetic background. This study holds the great promise of shedding light on the evolution of HIV-1, a virus that has been a threat to human health over the past decades and is known as a master evolver.

Beside science and coding, I really enjoy travelling and seeing new places to get to know its history, culture, and food. Meeting new people and having small chats with them is another activity that I cannot resist. If there has been one motto that I have been sticking to throughout my life it’s that I never say “no” to new experiences; our experiences are what make us who we are today after all.

Host institution:
University of Zurich (UZH), Switzerland
Local supervisor:
Prof. Dr. Karin Metzner (UZH)
Local co-supervisor:
Prof. Dr. Niko Beerenwinkel (ETH Zurich)
Project partner:
Work packages:
WP 1.3 Virus-host interactions
WP 2.1 Microevolution: Virus quasispecies

Karin Metzner
Niko Beerenwinkel

Project description

In the so far longest serial passaging experiments of HIV-1, virus populations are serially passaged in two T-cell lines (MT-2 and MT-4) and we observe significant differences in the fixation of viral variants in HIV-1 populations and the different dynamics of viral diversity in the two host cells. Furthermore, by switching the host cell, the swapped HIV-1 populations adapt quickly the dynamics of fixation and viral diversity according to the new environment. We will investigate the drivers – viral and host cell factors – of the differences in the accumulation of majority mutations and dynamics of viral diversity observed in MT-2 and MT-4 evolutionary lines.

Our objectives are:

  • (a) identification of differentially expressed genes between the two T-cell lines in uninfected and HIV-1 infected cells by conducting RNA sequencing,
  • (b) estimation of changes in kinetics of virus infection over time,
  • (c) determination of changes in viral fitness over time by dual infection/competition experiments.