Research Projects
Using CRISPR for Combination Therapy Screens

Many disease pathogeneses are contributed by multiple factors, involving a complex set of genes and pathways. Therefore, we believe that drug combination remedies can bring a larger therapeutic impact on patients. However, the conventional approaches for drug combination screens are not only expensive but also time-consuming; still, they only allow the testing of a limited number of drug combinations. The CombiGEM-CRISPR platform couples the versatile combinatorial genetics en masse technology and the programmable CRISPR-Cas9 system, and this allows high-throughput screening of genetic combinations mimicking the effect brought by drug combinations (Wong et al., Nature Biotechnology 2015; Wong et al., PNAS 2016; Zhou et al., Cell Reports 2020). This platform can rapidly assemble multiplex barcoded combinatorial genetic libraries, where each combination can be tracked based on their barcodes via high-throughput sequencing. To do drug combination screens, we select the guide RNAs (gRNA) targeting the drug-targeting genes and assigned a unique barcode to each of the gRNAs, then we build a multiplex barcoded gRNA library and identify the combined gRNA knockouts that give us the desired phenotype by doing a Next-Generation Sequencing (NGS) of the barcodes. Using this approach, our lab has successfully found synergistic drug combinations using the CombiGEM-CRISPR platform on various types of cancers and neurodegenerative diseases and is interested in improving this platform and screening for combination remedies in other complex genetic diseases.

The PhD project provides intensive training in high-throughput molecular biology, CRISPR-based genome editing, and NGS-based library screening and data analysis techniques.

Interested candidates should email Dr Alan Wong.

Professor ASL Wong, School of Biomedical Sciences

Professor Alan Siu-lun Wong is an Assistant Professor of the School of Biomedical Sciences at the University of Hong Kong (HKU). Before he joined HKU, he obtained his BSc and MPhil degrees in Biochemistry and Molecular Biotechnology from the Chinese University of Hong Kong in 2005 and 2007 respectively, and completed his PhD in Biochemistry at the Hong Kong University of Science and Technology in 2011. He joined the Synthetic Biology Group at Massachusetts Institute of Technology from 2012-2016 for postdoctoral training. Dr Wong was awarded with the Croucher Foundation Studentship (2008), the Butterfield-Croucher Award (2008), the Croucher Foundation Fellowship (2012), the Hong Kong Institution of Science Young Scientist Award in life science (2011), RGC Early Career Award (2016/2017), and NSFC Excellent Young Scientists Award (Hong Kong and Macau) (2020).

Biography
aslw@hku.hk

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.