School of Biomedical Sciences cordially invites you to join the following Post-doctoral Fellow (PDF) Seminar:

Date: 6 November 2024 (Wednesday)
Time: 4:00 pm – 5:00 pm
Venue: Seminar Room 2, G/F, Laboratory Block, 21 Sassoon Road
Host: Dr. Haifeng Fu

Light refreshments will be served. Please register via the below link by 4 Nov 2024 (Monday):
Registration: https://hku.au1.qualtrics.com/jfe/form/SV_0SrZL0eQEMgRr70

DNA tesseract
Dr. Chi Chin Simon Shiu (Post-doctoral Fellow)
[Supervisor: Professor Julian Alexander Tanner]

Nanostructures with intrinsic structural stabilization coupled with precise, programmable molecular positioning capabilities would have significant potential in materials science and medicine. Here, we develop a facet-based design where 16 equimolar canonical DNA oligonucleotides self-assemble to form a nested cube linked by trapezoids, denoted as a tesseract inspired by the four-dimensional hypercube. Cryogenic electron microscopy (Cryo-EM) and atomic force microscopy (AFM) analysis revealed a fully formed tesseract structure with exceptional stiffness. Circular dichroism and qPCR showed a consistent temperature of 84°C, significantly higher than other unmodified DNA nanostructures with hundreds of DNA strands. Such a simple and stable structure formed through bottom-up assembly of a small number of DNA oligonucleotides could have applications in drug delivery, and as a scaffold for structural investigation of small molecules by Cryo-EM.

Motor neuron-specific DLC1-i1 deficiency leads to neuromuscular defects in spinal muscular atrophy
Dr. Tianyuan Shi (Post-doctoral Fellow)
[Supervisor: Professor Martin Cheung]

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by the loss of the ubiquitously expressed survival motor neuron 1 (SMN1) protein but the mechanism underlying the selective loss of MNs remains unknown. Here, we found that DLC1 isoform 1 (DLC1-i1) is predominantly expressed in MN lineage and its reduced expression was detected in MNs derived from SMA patients’ urine-derived induced pluripotent stem cells (UiPSCs). SMA patients’ UiPSCs-derived neuromuscular organoids (NMOs) showed defective formation of neuromuscular junctions and increased cell death, which can be recapitulated by DLC1-i1 knockdown NMOs and overexpression of DLC1-i1 can rescue patients’ NMOs. Importantly, gene therapy with DLC1-i1 was more effective than SMN restoration in extending lifespan and improving locomotor activity in SMA mice. Altogether, our findings reveal that the neuromuscular defects in SMA are partly mediated by the loss of MN-specific DLC1-i1 expression and restoration of DLC1-i1 expression represents a more effective therapeutic approach for SMA.

All are welcome.