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

Date: 18 November 2025 (Tuesday)
Time: 4:00 pm – 5:00 pm
Venue: Seminar Room 2, G/F, Laboratory Block, 21 Sassoon Road
Host: Dr. Xiang Fang & Dr. Yolanda Liu

Light refreshments will be served. Please register via the below link by 17 November 2025 (Monday):
Registration: https://hku.au1.qualtrics.com/jfe/form/SV_cvTMmvwX3U9gSuG

Using computational tools to guide protein optimization: a case on designing the base-editor protein
Dr. Hoi Yee Chu (Post-doctoral Fellow)
[Supervisor: Professor Alan Wong]

The field of protein engineering is progressing in leaps with the current advancement in AI-driven models for learning protein sequences and properties. These models learn from a diverse source of information to produce protein folds and sequences similar to their natural counterparts. Applying these models to enzyme engineering enable us to rapidly design variants with customized properties alongside with high catalytic activity and thermostability. Here, we demonstrated how to use a blend of AI-models, physical based modelling tools and supervised machine learning models to guide us in engineering new base-editors evoAPOBEC1 and TadA-CBE variants. Our approach greatly reduced the efforts in high-throughput screening and downstream validation while expanded the diversity of the variants by introducing up to 10 mutations per iteration. Using our approach, we designed a panel of base-editors showing motif biases to improve editing precision. 

Modular chemical assembly of Bispecific T-Cell Engagers (BiTEs) for cancer treatment
Dr. Yuk Hei Chan (Post-doctoral Fellow)
[Supervisor: Professor Clive Chung]

Bispecific T-cell engagers (BiTEs) are potent immunotherapeutics with proven clinical success in hematological cancers. However, conventional BiTE production often relies on complex genetic engineering, limiting modularity and rapid prototyping. In this study, we introduce a novel chemical strategy for assembling BiTE-like constructs from commercially available monoclonal antibodies. Our lab-developed compound, NAAI, utilizes dual thiol-reactive groups and an alkyne handle for rapid, site-specific conjugation to reduced Fab fragments within 30 minutes, followed by a bioorthogonal click reaction with orthogonal linkers for efficient heterodimerization into functional BiTEs.

At the current stage, we have achieved alkyne installation on two Fab fragments (FabHER2 and FabCD3) with quantitative yield, as confirmed by intact protein mass spectrometry. We have also demonstrated successful click reaction with an azide proxy. Furthermore, ELISA analysis showed that these chemical modifications have minimal impact on the antigen-binding affinities of the two Fabs.

Moving forward, we are going to assemble functional BiTEs through click reaction with orthogonal linkers. One of these linkers include a customizable peptide sequence that could be tailored to target additional tumor antigens for enhanced avidity, recruit dendritic cells to potentiate immune response, or enable traceless fusion with immunomodulatory proteins for improved tumor penetration. This design greatly enhances modularity, and could introduce extra functionalities that directly address the limitations of existing BiTE constructs.

All are welcome.