Ana-Maria Cujba

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Academic and Work Experience Prior to Sept 2016 Programme Start

I obtained a MSci in Biochemistry (with Immunology) from University of Aberdeen with a year in industry at GlaxoSmithKline, Stevenage, UK. As part of an Aberdeen university team, I participated in the international Genetically Engineered Machine Competition at MIT, USA, where scientists across the world present innovative projects to address worldwide problems through synthetic biology. Our project aimed to develop an E. coli-based system to detect infections with the Trypanosoma parasite for people living in underprivileged rural places in Africa. 

PhD Programme – Year 1 – MRes and Project Rotations

During my first year here in the Wellcome Trust ‘Cell Therapies and Regenerative Medicine’ Four-Year PhD Programme, I tried different areas of research and learned new techniques to examine: 

1. the role of extracellular matrix niche factors on culturing primary human foetal hepatocytes with Dr Tamir Rashid;

2. regulatory T cells in Systemic Lupus Erythematosus and whether specific biomarkers can be associated with disease severity with Dr Giovanna Lombardi and Dr Cristinao Scotta;

3. regulators of one of the main pancreatic transcription factors, with the aim to find novel ways to generate stable and functional pancreatic organoids with Dr Rocio Sancho. 

Overall, I learnt how to work with very distinct cell lines, flow cytometry, functional assays, high-content imaging and new bioinformatic tools. The experience taught me that I want to combine bioinformatics with laboratory-based work during my PhD project.

PhD Programme – Years 2 to 4 – Doctoral Studies

My thesis work will focus on diabetes with supervisor Dr Rocio Sancho. Diabetes is characterised by the body's inability to regulate blood glucose. Pancreatic β-cells regulate glucose through insulin release. Monogenic Diabetes is a rare type of diabetes caused by gene mutations that make β-cells dysfunctional.

During my thesis work, I will be using induced Pluripotent Stem Cells (iPSCs) derived from patients with Monogenic Diabetes banked through the Human Induced Pluripotent Stem Cells Initiative (HipSci). The effect of the mutations will be investigated during pancreas development. The mechanism of action of the mutants will be investigated in vitro and in vivo. Through further understanding of the heterogeneity of Monogenic Diabetes phenotypes, this project aims to reveal more accurate detection targets and opportunities for personalised treatment.

Little Pancreas

Explanation: Pancreatic progenitor cells within an organoid stained for a cell membrane protein (Cytokeratin19) in green, transcription factor in red (PDX1 – pancreatic and duodenal homeobox 1) and the nuclei in blue. This organoid can be used to investigate pancreatic development in vitro to investigate differences between healthy and diseased tissue during early embryogenesis.

Hollow Sphere

Explanation: Brightfield image of a pancreatic progenitor organoid (mini-version of a pancreas at a very early development) which can be expanded up to millions of cells. Differences in their appearances and behaviors usually indicates differences in the cell types within them, viability and hunger, which helps us understand different subpopulations in early pancreatic development.

Mini-Party

Explanation: Brightfield image of pancreatic progenitor organoids that are expanding and differentiating in micro-wells in a suspension plate. Each well accommodates one 3D sphere. The organoid differentiation platform allows the differentiation of similar organoids, which could be used for drug screens.

Flower Power

Explanation: Brightfield image of a pancreatic progenitor organoid that self-organized into a distinctive morphology, with buds outgrowing from the initial sphere. The special morphology of this organoid informs us of the specific fate choices the organoid takes in further differentiation to islet cells that are resident in human pancreas ensuring hormone balance and insulin release.

Stick with You

Explanation: The sphere-like structure is a graft of a human pancreatic organoid transplanted onto the mouse liver tissue on the right green pebble-like structure. The green staining represents the pancreatic-specific PDX1 – pancreatic and duodenal homeobox 1 and the blue represents the cell nuclei. This pilot experiment investigates if human pancreatic organoids can survive and engraft into mouse tissue to determine if the organoid could be used for treating diabetes in mice. Once this proof-of-principle is established, investigation can begin to see if cell-based transplantation can provide needed relief of diabetes in humans.

Patient Avatar

Explanation: Brightfield image of a colony of human induced pluirpotent stem cells derived from the skin cells of a healthy human donor. Through a small non-painful biopsy punch, skin cells can be derived from any person and converted into these stem cells which can be cultured and studied indefinitely in laboratories. These cells are extraordinary models for investigating health and disease directly from human donors.

Coloured Moon

Explanation: Pancreatic progenitor organoid composed of proliferating cells in red (KI67), pancreatic cells in green (PDX1) and nuclei in blue. These organoids were cultured in a new type of highly characterised hydrogel that can be used for clinical-based applications in GMP-grade facilities.