timing of birth

INSTITUTION: Imperial College London
RESEARCHERS: Professor Mark Johnson, Professor Rachel Tribe, Dr Pei Lai, Dr Alice Varley, Jonathan Li

Timing of birth is key to a successful pregnancy. When this goes wrong, babies can be born too soon due to preterm labour, or too late because a mother fails to go into labour at the right time.

Both early and late labour are risky for the health of the baby and can sadly result in pregnancy loss, still birth or disability. To improve our ability to prevent preterm labour or dysfunctional labour, we need a better understanding of the biological processes that are responsible for the initiation of labour.

about the research

We are funding a research group at Imperial College’s laboratory at Chelsea and Westminster Hospital, which is focused on gaining a deeper understanding of the cellular mechanisms controlling healthy birth.

We know that, during pregnancy, the uterus is in a relaxed state and stretches to accommodate the growing fetus. At the maturation of the pregnancy, the uterus transitions to a highly contractile state to expel the baby. An understanding of what triggers this transition and how it can be controlled is central to understanding, and thus preventing, the early onset of labour.

Using uterine muscle (myometrium) taken from term pregnancies at the time of caesarean section, the research group explore the contribution of cyclic adenosine monophosphate (cAMP) – a key ‘signalling’ molecule that controls muscle function in many organs, including the myometrium. In particular, the research investigates the role that cAMP and its effectors may have in the fundamental transition of the uterus from a relaxed to a contractile state.

meet the team

Borne continues to fund a team of talented young scientists working together under the scientific guidance and support of Professor Mark Johnson and Professor Rachel Tribe (King’s College London).

Dr Pei Fong Lai is an experienced early career researcher who provides day-to-day supervision of the research group. She is currently writing up her research with myometrial tissue samples, investigating how cAMP acts to keep the womb relaxed, allowing the baby to grow until it is safe to be born.

“I have used data from my work funded by Borne for writing grant applications, as well as presented them for international peer discussion at scientific meetings and in journal publication.”

– Dr Pei Fong Lai

Dr Alice Varley is currently writing up her PhD thesis, having generated some exciting data using cutting edge imaging techniques to demonstrate complex intra-cellular compartmentalisation of cAMP, under the guidance of Professor Manuela Zaccolo at the University of Oxford.

PhD student Jonathan Li is the recipient of the Robert McAlpine Studentship Award. He will complete his doctorate this year on the changes in myometrial cell function that are triggered by cAMP signalling as the uterus transitions from quiescence to contractility.

UPDATES & IMPACT

In spite of delays caused by the pandemic, the research group continues to make progress, and outcomes from the studies have encouraged an exciting collaboration amongst experts in the field.

Unsurprisingly, the last year has impacted on the team’s work due to the lengthy suspension of non-Covid research and restricted access to labs. However, the team has continued to be productive by analysing experimental data, drafting research articles for publication and on returning to the laboratory completing essential experiments, utilising tissues and cells from their unique biobank.

Several publications in 2020 highlighted the key role cAMP and down-stream effectors play in modulating uterine muscle preparation for labour. The success of the cAMP studies to date has led to a collaboration amongst the leading experts on cAMP signalling – Borne Chief Scientific Officer Professor Mark Johnson (Imperial College London); leading reproductive physiologist Professor Rachel Tribe (King’s College London); cardiac specialist with expertise on compartmentalised cAMP signalling in the heart, Professor Manuela Zaccolo (Oxford University); and molecular pharmacologist and cAMP signalling specialist Professor George Baillie (Glasgow University).

The collaboration has culminated in the joint application for competitive funding from the Research Councils to take their work forward on a larger scale. The progress of the cAMP research embodies Borne’s objective of pump priming promising new lines of scientific investigation and attract more talent and funding to this critical area of need.

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