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• R0152: Pluripotency, reprogramming and mitochondrial biology during early human development
• R0153: Mitochondrial DNA Disorders: Is there a way to prevent transmission?

R0152: Pluripotency, reprogramming and mitochondrial biology during early human development

Licence holder: Professor Alison Murdoch

IVF treatment usually results in multiple embryos of variable quality. The best quality are selected for replacement in the womb and couples are given the option to freeze additional good quality embryos. Embryos that are not used for treatment can be donated to research. The ultimate aims of our research is to develop IVF-based techniques for the prevention and treatment of disease and to better understand the impact of laboratory processing on early development.   This includes making stem cells from embryos.

In addition to the treatment of infertility, IVF-based techniques can be used to prevent transmission of genetically inherited disease. Abnormalities of the genes in mitochondria (the power sources in cells) are an important cause of genetic disease, which can cause still births or death early in life. Disease associated with mutations in the mitochondria are transmitted from mother to child, and a woman who is herself relatively symptom-free can give birth to severely affected children. A specific aim of our research therefore is to investigate the feasibility of using IVF-based techniques to prevent transmission of mitochondrial disease and to better understand how mitochondrial DNA divides itself between cells during early development. 

This research will study the processes that occur in the human egg just before fertilisation and over the next few days. This involves laboratory studies on the way that eggs start to divide using different stimulation methods.  We will also take a nucleus from a cell donated by adult volunteers, put it into an egg then stimulate the egg to divide so that the genetic material in the donated nucleus is reprogrammed.  We will transfer the nucleus from one abnormally fertilised egg to another so that we can study how the mitochondria are passed between cells.  We will derive embryonic stem cells from embryos and from reconstructed embryos.

In order to interpret and improve the results we need to optimise the processes under which we grow the embryos. We understand little about how in vitro manipulations might influence the early human development. An integral aim of our research therefore, is to ask whether these processes are affected by laboratory procedures such as in vitro culture and freezing.

Stem cells can be derived from embryos and reconstructed embryos and it is recognised that these cells may be useful in the treatment of serious disease.  For clinical use, they will need to be grown under specific defined conditions.  This needs modification of the routine IVF methods.  We therefore aim to establish a system for deriving embryonic stem cells which is compatible with their future use in clinical treatment. 

We believe that our research will lead to a better understanding of early developmental events and to improved treatments for infertility and for a range of debilitating diseases.

• Research Licence Committee Minutes (98 Kb)

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R0153: Mitochondrial DNA Disorders: Is there a way to prevent transmission?

Licence holder: Dr Mary Herbert

Mitochondria are organelles that convert the food we eat into energy. There are many mitochondria in every cell of our body. Each mitochondrion has its own DNA which is separate from 'nuclear' DNA. Nuclear DNA contains genetic information in the cell which influences the make up of the whole body, however mitochondrial DNA only provides instructions on how mitochondria behave.

If these genes are damaged an affected person may develop severe disease leading to disability and death. Mitochondrial genes are inherited only through the mother who may pass the disease on to her children. At present no treatment for mitochondrial diseases exists.

Previous studies in mice have shown it is possible to prevent the transmission of mitochondrial disease by moving the pronuclei (pronuclei ultimately develop into an embryo's nucleus containing the embryo's 'nuclear' DNA) from an egg containing bad mitochondria to another egg which only contains good mitochondria.

In experiments conducted on mice, eggs developed normally and non affected mice were born after the procedure. These experiments are very encouraging but there are many differences between mouse and human eggs.

We are proposing to determine if moving the pronuclei could ever be used for our patients by taking abnormally fertilised human eggs (which cannot be used for treatment) and transferring the pronuclei from one egg to another. Following this transfer we would monitor the possible carry-over of mitochondria between eggs and will determine whether the egg then develops normally.

We hope that these studies will provide vital information as to whether we could ever prevent the transmission of mitochondrial diseases from mother to child.

• How the decision to licence this clinic was made (32.01 Kb)
• Extended summary (20.24 Kb)

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