Research Laboratory of Alan Christoffels

PROF ALAN CHRISTOFFELS

PhD, M.ASSAf
Director & DSI/NRF Research Chair in Bioinformatics and Health Genomics
Director of SA MRC Bioinformatics Unit
South African National Bioinformatics Institute
University of the Western Cape

Contact Details

    • Telephone: +27-(0)21-9592969
    • Fax: +27-(0)21-9592512
    • Email: alan(at)sanbi.ac.za
    • Skype: alan.christoffels
    • Website: christoffels.sanbi.ac.za

RESEARCH PROJECT THEMES

Theme Project
Pathogen genomics ·         In collaboration with the Tygerberg MRC Unit, we are developing methods to analyse high throughput sequencing data for microbial genomes. ·         Identification of novel drug targets in pathways known to contain drug resistant genes. ·         Predicting the interaction networks between human and mycobacteria ·         Identification of operons & non-coding RNAs to understand gene regulation in pathogen genomes.
Pathogen surveillance ·         Developing systems to support reproducible analyses ·         Development of global standards for data sharing and integration ·         Public Health Alliance for Genomic Epidemiology (PHA4GE)
Drug discovery ·         Identifying drug molecules against multi-drug resistant M.tuberculosis ·         In partnership with the School of Pharmacy at UWC, delineate the pharmacokinetics of drugs in response to host genetic factors ·         In partnership with the School of Pharmacy at UWC, use of machine learning techniques to prioritise molecules in natural compounds.

RESEARCH PROJECTS

The projects below underpin our translational work:

Tuberculosis

A comprehensive research programme is underway that includes investigating genetics determinants in both host (Human) and pathogen (Mycobacterium tuberculosis) to understand drug resistance, and protein structure determination to inform patient-centric drug design. These findings inform the development of a scientific workflow management system to support reproducible high throughput computational experiments. These workflows form the basis of our COMputational BActerial analytical toolkit for Tuberculosis research (COMBAT-TB) (www.combattb.org) initiative to deploy analytic tools across the African continent. This analytics platform has been customised for SARS-CoV-2 analysis.

Biobanking

In collaboration with Dr Dominique Anderson at SANBI, we continue to strengthen our biobank software capabilities so that genetics data and biospecimens can be curated and stored.

Applications of Machine Learning methods to protein-protein interactions

Recently we used quadruplet amino acids as a feature in training model for protein interactions. We are extending this work to improve on the accuracy of our models with small datasets.

RESEARCH COLLABORATIONS

    1. Develop a biobank informatics management system
Collaborating Parties:
Dr Dominique Anderson – SANBI, UWC and Africa CDC

Nature and Purpose:
Development of a laboratory management system for infectious disease labs that will integrate with other biobanking tools.

Output in the last 12 months:
Added a freezer monitoring schedule. Submitted a book chapter on biobank software for low and middle income countries.

  1. Analyzing genetic networks in M.tuberculosis
Collaborating Parties:
Prof Rob Warren – University of Stellenbosch
Dr Hocine Bendou – SANBI, UWC

Nature and Purpose:
Identification of Operons: We rewrote an algorithm previously published by a team at Johns Hopkins University. Identification of non-coding RNAs.

Output in the last 12 months:
Our Operon detection algorithm has been tested with different metrics, and is currently benchmarked against two international methods. Using a sequence conversation approach and a RNA folding approach, we are identifying putative small RNAs.

  1. Identification of novel drug targets for drug resistant tuberculosis
Collaborating Parties:
Profs Samantha Sampson and Rob Warren – University of Stellenbosch Dr Ruben Cloete – SANBI, UWC
Prof Sarel Malan – School of Pharmacy, UWC
Prof Valery Danilenko and Dr Dmitry Maslov – Vavilov Institute of General Genetics, Russia

Nature and Purpose:
Current TB drugs are more than 30 years old and have unacceptable efficacy and safety profiles, emphasising the need for new drugs. In this regard we published a paper on kinase inhibitors in M.tuberculosis, and efflux pump inhibitors.

Output in the last 12 months:
We continue to refine our computational screening system. And submitted a funding application via the BRICS-country funding mechanism.

  1. Computational Bacterial analytical toolkit for Tuberculosis (COMBAT-TB)
Collaborating Parties:
Profs Samantha Sampson and Rob Warren – University of Stellenbosch
Peter van Heusden – SANBI-UWC

Nature and Purpose: Develop a computational platform to store Tuberculosis omic data and to provide a visualisation tool.

Output in the last 12 months: Added further analysis tools and a user manual. Our manuscript was published in mSphere Journal.

  1. Biosecurity Preparedness in Africa
Collaborating Parties:
Dr Dominique Anderson – SANBI, UWC Global Consortium on emerging infectious diseases (www.getafrica.org).

Nature and Purpose:
We aim to establish  infrastructure and research capacity to respond to highly infectious emerging Pathogens.

Output in the last 12 months:
We have reviewed the information security policies at SA Universities with a view to propose guidelines for data management that impacts biomedical researchers.

  1. Public health alliance for genomic epidemiology (PHA4GE)
Collaborating Parties:
Africa CDC, Oxford University, Washington University, University of Melbourne, USA CDC, University of Birmingham UK, University of British Columbia and BC Centre for Disease Control, Broad Institute in Boston, and H3Africa.

Nature and Purpose:
The PHA4GE consortium was established to bring Bioinformatics closer to Public Health – to build data standards.

Output in the last 12 months:
PHA4GE data standards working group developed a metadata standard for COVID-19 biospecimen collection.

  1. African Genomics Archive
Collaborating Parties:
Africa CDC

Nature and Purpose:
To establish a data platform in Africa to manage disease surveillance data with a view to strengthen public health institutes.

Output in the last 12 months:
A series of workshops to gather information on various use cases.