"Stemamers": evaluation of slow off-rate aptamers (Somamers) in stem cell biotechnology.

Induced pluripotent stem cells have unprecedented biotechnological potential, from providing physiological models for the identification of pharmaceutical leads to the production of defined tissues for cell therapy. A key barrier to the large scale industrial exploitation of these potentials stems from the two-dimensional, demanding culture format and the cost and irreproducibility of the biological additives to culture media. These challenges could be addressed by the modulation of stem cell behaviour in vitro by ligation of their cell-surface receptors by high-affinity nucleic acid ligands. SomaLogic has developed such aptamers using their proprietary SOMAmer technology, and this project will build on a research collaboration framework agreement recently concluded between them and Oxford to evaluate their potential. The student would benefit from the support of two other collaborative projects currently underway between the two groups.
Depending on progress, the student would have the opportunity to evaluate Somamers against other cell surface molecules involved in stem cell maintenance and differentiation.

Importantly, the student would also use the unique SOMAmer reagents to explore the biology adherens junctions in the physiology of stem cells. Using a combination of confocal microscopy and proteomic techniques in use in the James Lab, they would explore the kinetics of the formation of adherens junctions in both primed and naïve pluripotent stem cells, and the effect of their disruption by Somamers to e-Cadherin on down-stream signalling pathways. The results would not

only shed critical light on the maintenance of the pluripotent states, but also offer further avenues for biotechnological manipulation.

Principal Location: Sir William Dunn School of Pathology, University of Oxford

Non-academic partner location: SomaLogic is located in a well-designed facility in Boulder, Colorado and has about 170 employees. The facility has approximately 20,000 square feet of laboratory space, separated into two buildings for technology development, aptamer screening, assay development and assay execution, and chemistry. Training in the latest methods of nucleic acid chemistry and biotechnology, including the use of aptamers in high-sensitivity proteome detection arrays will be provided during the residency at SomaLogic.

This project is supported through the Oxford Interdisciplinary Bioscience Doctoral Training Partnership (DTP) BBSRC Industrial CASE (iCASE) studentship programme. The student recruited to this project will join a cohort of students enrolled in the DTP's interdisciplinary training programme, and will be able to take full advantage of the training and networking opportunities available through the DTP.