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Summer Studentships 2022 Maia Kazakova

Researcher: Maia Kazakova

Location: University of Edinburgh

2022 FRAME Summer studentship winner Maia Kazakova Garcia, studying at the University of Edinburgh, was awarded £3016 for her project looking to improve induced pluripotent stem cell programming to make human-relevant drug development and disease research more accessible.

The problem

Stem cells have always been of interest in research due to their ability to differentiate into different specialised cell types. They are undifferentiated cells found in embryos and adult organisms which have the potential to grow into any type of body, dependant on the environment they are in. Their potential to regenerate tissue lost by injury or disease has been utilised in medical science and stem cells are used today in bone marrow transplants for treating leukaemia and non-Hodgkin’s lymphoma, stem cell therapy has also had some success in treating other conditions such as stroke symptoms and arthritis. Historical stem cell research has led to the development of new in vitro models, including the development of 3D organoids which are used in research today often replacing animals. Whilst we have stem cells throughout our body in locations such as the brain, bone marrow, blood, blood vessels, and liver, they can be tricky to obtain and are more limited in their ability to differentiate than embryonic stem cells. Medical advances as a result of the availability of pluripotent cells have therefore been conducted with embryonic stem cells, which raises ethical concerns around the destruction of human embryos. However, in 2006, Japanese scientists created the first induced pluripotent stem cells from adult body, or somatic, cells in the lab. They used four proteins involved in DNA regulation called ‘transcription factors’ to reprogramme the somatic cells back into a state similar to embryonic stem cells, one of these transcription factors was Sox2.  Since then scientists have been developing and testing methods to reprogramme various adult human body cells to become induced pluripotent stem cells. These cells are ‘pluripotent’ in the same way as embryonic stem cells, which means they have the potential to differentiate into any type of body cell and therefore replace the use of embryonic stem cells in research. Unfortunately, this reprogramming process remains inefficient, with cells not fully reprogrammed, and therefore the practice of creating them remains expensive and time-consuming. This has a knock-on effect limiting their use in routine research and drug discovery where other methods, possibly ones using animals, are cheaper and more reliable.

The project

In her project, Maia is looking to understand the role of transcription factor Sox2 in reprogramming by studying how Sox2 interacts with DNA. She will do this by looking at whether Sox2 can access DNA in condensed conformations and by comparing Sox2 to a similar transcription factor Sox9 to compare and contrast the two. The aim of this is to understand more about the limitations of Sox2 in order to potentially engineer new proteins which can carry out the same reprogramming function more efficiently. If achievable, these new proteins could improve the induced pluripotent stem cells creation processes, making the production of these cells for research more reliable, cost-effective and sustainable. This could radically speed up and improve research into induced pluripotent stem cell and genetically engineered characterisation and maintenance, and their potential across many areas of research and testing.

The potential

If induced pluripotent stem cells processes were faster and more effective, they could provide physiologically relevant human cells that could be utilised in basic research, drug discovery, safety testing, regenerative medicine and disease research. The benefits of these cells are their human relevance, adaptability, potential to be genetically manipulated, also their disease-relevance if sourced from the patient, potentially providing scalable quantities of tissue for research, and finally the potential they have in the future to pave the way to personalised therapies specific to individual patients. Induced pluripotent stem cells could hold the key to the provision of much-needed human tissue for research and testing, research where many animals and animal cell lines are still routinely used. Not only do they have the potential to reduce animal testing they also provide more human-relevant or patient-relevant models for understanding disease and testing therapies in a way that current animal models cannot.

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