Farid GHADESSY

Protein and Peptide Engineering and Research Laboratory (P2ERL)
PhD – Biochemistry/Chemistry, University of Sheffield (UK)
Email: fghadessy@imcb.a-star.edu.sg
SUMMARY
Farid Ghadessy is a Senior Principal Investigator at the Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore, where he co-leads the Protein and Peptide Engineering and Research Lab (P2ERL) alongside his colleague, Christopher J. Brown. His research focuses on the engineering and discovery of novel biotherapeutics and molecular diagnostic enzymes using directed evolution approaches.
Farid’s work emphasizes technology development to create biologics, such as peptides and miniproteins, that target dysfunctional signaling pathways. A key aspect of his research involves developing and utilizing a range of directed evolution methodologies for protein engineering and selection. These same approaches are also applied to re-purpose enzymes for industrially relevant applications, particularly in designing “greener” enzyme alternatives for pharmaceutical synthesis.
In addition to his work on biotherapeutics, Farid’s research extends to the development of innovative biosensing platforms. His team focuses on modular protein biosensors designed for efficient drug screening and diagnostic applications.
Farid is also the co-founder of AbAsia Pte Ltd, a reagents and protein expression company, further reflecting his commitment to bridging research with practical, industry-driven solutions.
RESEARCH
Protein and Peptide Engineering and Research Laboratory (P2ERL)
Our team's primary focus is on discovering novel modalities, such as macrocyclic peptides and mini-proteins, to perturb intracellular biological interactions of therapeutic interest. Specifically, we target macromolecular surfaces that are challenging for small molecules to bind. We employ various display technologies, including chemically modified phage and yeast libraries, to efficiently explore chemical and structural space and discover these molecules. Characterization is performed using biophysical and structural methods. We have also begun to explore the application of lentiviral based libraries to deliver protein fragments to perturb phenotypes of interest with the aim of identifying novel druggable sites.
Our research interests include developing techniques to enhance the functionality of these molecules and enable targeted delivery for target validation and therapeutic modeling studies. For example, our research has explored the use of mini-proteins in 3D cellular culture and animal systems to model potential cellular effects. Molecules exhibiting desirable properties can serve as scaffolds for therapeutic development, guiding the design of novel treatments. Additionally, we have investigated the fusion of mini-proteins with protein domains of orthogonal functionality, such as E3 ligases, to enable extended modes of inhibition and catalytic degradation of multiple target molecules.
PUBLICATIONS
- Engineering cell-free systems by chemoproteomic-assisted phenotypic screening.
Levitskaya Z, Ser Z, Koh H, Mei WS, Chee S, Sobota RM, Ghadessy JF.
RSC Chem Biol. 2024 Mar 6;5(4):372-385. - Expanding the DNA editing toolbox: Novel lambda integrase variants targeting microalgal and human genome sequences.
Siau JW, Siddiqui AA, Lau SY, Kannan S, Peter S, Zeng Y, Verma C, Droge P, Ghadessy JF.
PLoS One. 2024 Feb 13;19(2):e0292479. - Thermostability enhancement of polyethylene terephthalate degrading PETase using self- and nonself-ligating protein scaffolding approaches.
Sana B, Ding K, Siau JW, Pasula RR, Chee S, Kharel S, Lena JH, Goh E, Rajamani L, Lam YM, Lim S, Ghadessy JF.
Biotechnol Bioeng. 2023 Nov;120(11):3200-3209.
- Visualizing intracellular target antigens in live cells.
Ueda H, Dai Y, Ghadessy F.
Trends Cell Biol. 2023 Apr;33(4):277-279.
- Halogenation of Peptides and Proteins Using Engineered Tryptophan Halogenase Enzymes.
Sana B, Ke D, Li EHY, Ho T, Seayad J, Duong HA, Ghadessy FJ.
Biomolecules. 2022 Dec 8;12(12):1841.
- A “spindle and thread” mechanism unblocks p53 translation by modulating N-terminal disorder.
Kaldmäe M, Vosselman T, Zhong X, Lama D, Chen G, Saluri M, Kronqvist N, Siau JW, Ng AS, Ghadessy FJ, Sabatier P, Vojtesek B, Sarr M, Sahin C, Österlund N, Ilag LL, Väänänen VA, Sedimbi S, Arsenian-Henriksson M, Zubarev RA, Nilsson L, Koeck PJB, Rising A, Abelein A, Fritz N, Johansson J, Lane DP, Landreh M.
Structure. 2022 May 5;30(5):733-742.e7.
PATENTS
- Mutants of the bacteriophage lambda integrase (US10344301B2)
The present invention refers to lambda integrases comprising at least one amino acid mutation at positions 43, 319 and 336 of the lambda integrase as set forth in SEQ ID NO: 1. The invention further refers to nucleic acid molecules comprising the nucleotide sequence encoding the mutant lambda integrase and to host cells containing these nucleic acid molecules. The invention also refers to methods of recombining a nucleic acid of interest into a target nucleic acid in the presence of the mutant lambda integrase and sequence specific recombination kits. - p53 activating peptides (US9517252)
The present invention is directed to p53 activating peptides. The present further describes methods for generating these peptides and the use of these peptides.
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