Effects of Human Milk MicroRNAs on Early Brain Development: An In Vitro Study

Eligibility: UK/International (including EU) graduates with the required entry requirements

Duration: Full-time – between three and three and a half years fixed term

Application deadline: 25 Aug 2026

Interview date: Will be confirmed to shortlisted candidates

Start date: January 2027

For further details contact: Assistant Professor Isadora Clivatti Furigo

Introduction

Lactation contributes to the optimal development and growth of the infant's brain. The specific component of human milk responsible for this benefit is unclear. However, an emerging theory suggests that exosomes containing neuromodulating microRNAs (miRNAs) present in human milk (HM) play a crucial role in this process, although studies have limited its analysis to only mature milk. HM is a dynamic fluid consisting of colostrum, transitional, and mature milk stages. We hypothesise that the miRNA profiles of the three milk stages differ, and preterm delivery alters these profiles, potentially impacting postnatal infant neurodevelopment. This project will address this critical knowledge gap by combining early postpartum clinical and hormonal assessments of breastfeeding women using cutting-edge neurodevelopmental cell models.

Project details

The aims are:

Comprehensively characterise the miRNA profile of exosomes isolated from the three major HM types from mothers who delivered at term or prematurely;
Determine the influence of maternal factors such as age, parity, body mass index, and key lactation hormones such as oestrogen, progesterone, and prolactin on HM miRNA composition; and
Investigate the impact of highly expressed HM miRNAs on postnatal neurodevelopment, using 2D human cortical neuron models and 3D neural networks derived from human induced pluripotent stem cells (iPSC).

Improved understanding of the role of HM miRNAs may lead to interventions supporting brain development in preterm infants and potentially mitigate cognitive challenges associated with premature birth.

Neurodevelopmental disorders affect up to 40% of preterm infants and 30% of small-for-gestational-age infants, leading to long-term disabilities(1,2); I propose that human milk may alleviate these disorders through microRNAs (miRNAs), which are non-coding RNAs that regulate gene expression. Neurodevelopmental disorders may arise from abnormalities of neurogenesis, myelination, neuronal energy metabolism, synapse formation, or cortical folding, and treatments are lacking to rectify these alterations. Human milk (HM) has therapeutic potential for preterm infants: it has been shown to improve brain architecture, white matter development, and cognitive performance in term and preterm infants(3–10). However, it is unclear how these effects are mediated, and one mechanism involves miRNAs, which are non-coding RNAs that regulate gene expression(11). MiRNAs are abundant in HM(12–14), where they are localised in small extracellular vesicles termed ‘exosomes’. HM exosomes have the potential to deliver miRNA cargo to the infant's brain as they protect ingested miRNAs from gastric digestion and can cross the blood-brain barrier(15,16).

The impact of miRNAs on neurodevelopment has been explored during foetal development, with the discovery of miRNAs mediating neural induction and differentiation(17). However, less is known about the impact of HM miRNAs on postnatal neurodevelopment. One study analysed exosomal miRNAs in term and preterm HM and found that miR-3168 was the most upregulated miRNA that targeted genes mediating early neurodevelopment(18). However, this study involved only mature HM from mothers in established lactation, which limits its findings. Indeed, HM is a dynamic fluid that adapts to meet the requirements of the developing neonate and infant, and comprises: colostrum (produced on postpartum days 1-3); transitional milk (postpartum days 4-13); and mature milk (postpartum days 14 onwards). Information is currently lacking on the differences in exosomal miRNA content between these HM types, and I hypothesise that colostrum, transitional milk, and mature milk from mothers with preterm or term infants have distinct miRNA profiles with potentially selective neurodevelopmental effects.

In support of this, a study showed that human colostrum stimulated a marked increase in neuronal outgrowth from olfactory bulb explants when compared to mature milk from the same mother(19). The goal of this project is to advance knowledge in this area and improve understanding of the neurodevelopmental role of miRNAs present in colostrum, transitional milk, and mature milk by undertaking the clinical and cellular studies described below.

Objectives

To perform:

Comprehensive characterisation of the changes in HM miRNAs from the colostrum phase through to the establishment of
mature milk production in mothers with preterm (born before 37 weeks gestation) and term infants.
Assessment of maternal demographic, clinical, and hormonal determinants of HM miRNA composition.
Investigate the influence of exosomes isolated from colostrum, transitional milk and mature milk on the development and function of cultured neuronal cells and a human iPSC-derived brain organoid.

The student will focus on the development of a brain organoid model to investigate the influence of exosomes isolated from colostrum, transitional milk and mature milk on the development and function of cultured neuronal cells and a human iPSC-derived brain organoid.

Funding

Tuition fees and bursary.

Benefits

The successful candidate will receive comprehensive research training including technical, personal and professional skills. All researchers at Coventry University (from PhD to Professor) are part of the Doctoral and Researcher College, which provides support with high-quality training and career development activities.

Entry requirements

A minimum of a 2:1 first degree in a relevant discipline/subject area with a minimum 60% mark in the project element or equivalent with a minimum 60% overall module average.

PLUS

The potential to engage in innovative research and to complete the PhD within 3.5 years.
A minimum of English language proficiency (IELTS academic overall minimum score of 7.0 with a minimum of 6.5 in each component).

Additional requirements

Previous experience with cell culture and sequencing analysis is desirable.

How to apply

To find out more about the project, please contact Assistant Professor Isadora Clivatti Furigo.

All applications require full supporting documentation, a covering letter, plus a 2000-word supporting statement showing how the applicant’s expertise and interests are relevant to the project.

Apply to Coventry University