Mira Kassouf

I am a senior Postdoctoral Researcher working with Prof. Doug Higgs in the Gene Regulation Group at the MRC Weatherall Institute of Molecular Medicine, University of Oxford. We study how genes are switched on and off in development, differentiation and disease.

It is widely accepted that this involves the interaction between at least three fundamental regulatory elements: enhancers, promoters and insulators. Activation information is transferred from enhancers to their cognate promoters often by coming into close physical proximity to form a “transcriptional hub” containing a high concentration of TFs and co-factors. The mechanisms underlying these stages of transcriptional activation are not fully explained.

My research focuses on what characterises the DNA sequence underlying cis-regulatory elements in mammalian genomes as well as their sequence orientation and position within a regulatory landscape and how these characteristics influence gene regulation.

In more detail

Throughout my academic training, I have been interested in how genes are switched on and off, the outstanding question that underlies the complexity of living organisms. Addressing the topic from both, the regulatory protein and DNA sequence perspectives, I have used the hematopoietic system (and red cells in particular, erythropoiesis) as the model of choice:

1- In my D.Phil and first postdoctoral project, I focused on a tissue-specific transcription factor (Tal-1) and studied the effect of its recruitment to regulatory DNA sequences on gene regulation genome-wide. In the process, I have developed an in depth theoretical knowledge and technical expertise that allowed me to maintain and genetically manipulate mouse Embryonic Stem (ES) cells, and produce and analyse both in vivo and in vitro mammalian models to test my hypotheses.

2- In my current research position, I supervise and work with a team of D.Phil students, visitings trainees and postdocs on what drives enhancer-promoter interaction. Using state of the art cellular and molecular biology tools, I generate genetic models that dissect and perturb enhancers, promoters and boundary elements at the mouse alpha globin locus to understand the rules that govern their interactions. I examined in detail the effect of sequence and context perturbation on the function of a single enhancer as well as the cluster of enhancer-like elements (the super-enhancer), on the promoters and CTCF sites at the alpha-globin locus. In the process, I have developed an in vitro miniaturised mouse ES hematopoietic differentiation system for high throughput manipulation and screening of genetically-modified mouse ES cells.

I will continue my pursuit of unravelling how the linear organisation as well as the sequence orientation of genomic elements impacts on gene regulation, both in normal and pathological contexts.

Collaborations

The Dark Matter Project

In collaboration with Prof Jef Boeke (NYU Langone Health), we synthesise variants of the mouse α-globin gene to replace the naturally-occurring α-globin gene in mice and mouse cell lines in order to explore their effects on the production of α-globin. This approach will allow us to further our understanding of how gene expression is regulated in general  as well as gain invaluable insight into the underlying causes of α-thalassemia, help develop strategies to correct the disease.

MRC National Mouse Genetics Network Technology Cluster

Along with Prof Ben Davies (The Francis Crick Institute), I am a co-investigator on an MRC grant dedicated to promoting and enhancing use of mouse models for addressing fundamental questions in gene regulation where complex landscapes are involved as well as for modeling human genetic diseases.

The Oxford-Berlin Research Partnership

In collaboration with Dr Daniel Ibrahim (Max Plank Institute and the Charité-BIH), we set out to design an approach that overcomes the current limitations of the existing Enhancer/Promoter (E/P) sequence compatibility screening in well-characterised loci in mouse embryonic stem cells (mESCs) in the context of near-native chromatin environments. With this collaboration, we aim to exchange expertise and reagents to expand our datasets and consolidate our findings in different experimental testbeds.

Other roles

INNOVATION FORUM OXFORD

I am co-founder and current president of Innovation Forum Oxford, a non-for-profit organisation, part of a global organisation, run by "scientists for scientists" with the mission to inspire, educate, and empower scientific researchers to recognise the value of their research and harness their findings for the benefit of human health. Lowering the barriers for knowledge exchange and collaborations with the outside world (industry, NHS, policy makers, enablers)  is at the heart of the events we design and deliver. This has been acknowledged by the University of Oxford as we were awarded the Knowledge Exchange Seed Fund for our 2018 workshop series (ACE saturdays) and three independent nominations (MRC WIMM, MSD Business Development Office, OUI) for the 2018 Vice-chancellor Inaugural Innovation Award. Interview

WE ACE

With a focus on shining the light on Women Entrepreneurs (WE), I created WE ACE 2020; the programme had a personalised approach to addressing the needs of women at various stages in their early entrepreneurial journey, equipping participants with leadership and negotiation skills. After 4 years of running and more than 70 participants, the programme created a community of trailblazing women entrepreneurs in the health and life sciences.

Oxford University Knowledge Exchange Seed Fund 

I am the chair of the committee for the KE Seed fund. This is an internal grant scheme designed to support Knowledge Exchange activities and projects. It is supported by the University’s Higher Education & Innovation Fund (HEIF) award to ‘support and develop a broad range of knowledge-based interactions between universities and the wider world, which result in economic and social benefit to the UK. ’

Messages from WIMM women in STEM

Financial Times Article - Patience in the workplace

education

After completing my BSc at the American University of Beirut (AUB), I was awarded Karim Rida Said Foundation (KRSF) scholarships to complete my graduate studies in the UK; an MSc in Human Genetics at Brunel University and a D.Phil at the University of Oxford. 

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