Molecular Microbiology and Biotechnology

Group Leader

João Gonçalves

PhD (1996) in Pharmacy (Microbiology), Universidade de Lisboa
Postdoctoral research at Harvard Medical School and Scripps Research Institute, USA
Associate Professor, Faculdade de Farmácia, Universidade de Lisboa
Group Leader, Molecular Microbiology and Biotechnology at iMed.ULisboa
Program Area Leader, Drug Discovery at iMed.ULisboa
 

The Research

Our main focus is to answer fundamental questions on the molecular mechanisms underlying, promoting and controlling infectious diseases. We developed cutting-edge research aiming to describe and control the interaction between the cell and the infectious agent. Our work on Mycobacterium tuberculosis drug resistance challenges to an effective tuberculosis disease control. Knowledge emerging from these studies has been explored to develop innovative molecular strategies for control of bacterial pathogens. With bacteriophage-bacterial cell interactions, we focused on probing the function of the two holin-like proteins of bacteriophage SPP1. We also emphasized our work on factors that are associated with the control of HIV replication and latency. The use of rational protein engineering helped us to modulate antiviral defenses. We developed the first potent and broad VL sdAb fusion inhibitor of HIV infection. Our study gives insights into engineering strategies that could enhance the development of antiviral drugs. In the case of latency, we have demonstrated that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and develop improved therapies for latent HIV-1 infection.

General representation of group research activities and goals.

Ongoing Projects

Source: FCT (PTDC/QEQ-MED/4412/2014)
Title: Towards the development of innovative highly effective action of anti-HIV peptides.
PI: Salomé Sousa; Participant: J Goncalves
Period: 2016-2018

Source: COMPETE2020 and FCT (SAICTPAC/0019/2015)
Title: POINT4PAC – Precision Oncology by Innovative Therapies and Technologies
PI: CMP Rodrigues
Period: 2017-2019

Source: (PTDC/BIM-MEC/6631/2014)
Title: Vif in Cancer Therapy
PI: Isabel Barahona; Participant: J Goncalves
Period: 2016-2018

Source: Shire Pharmaceuticals
Title: Immunogenicity against Agalsidase in Pompe’s patients
PI: Joao Goncalves
Period: 2017-2020

Recent Most Relevant Publications

Coll F, Phelan J, Hill-Cawthorne GA, Nair M, Mallard K, Ali S, Abdallah A, Alghamdi S, Alsomali M, Ahmed A, Portelli S, Oppong Y, Alves A, Bessa T, Campino S, Caws M, Chatterjee A, Crampin A, Dheda K, Furnham N, Glynn J, Grandjean L, Há D, Hasan R, Hasan Z, Hibberd M, Joloba M, Jones-López, Matsumoto T, Miranda A, Moore D, Morcillo N, Panaiotov S, Parkhill J, Portugal I, Penha C, Perdigão J, Rchiad Z, Robledo J, Sheen P, Sesha N, Sirgel F, Sola C, Sousa E, Streicher E, Viveiros M, Warren R, McNerney R, Pain A, Clark T. Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis. Nat Genet 2018; 50: 764

Aguiar S, Dias J, Manuel AM, Russo R, Gois PMP, da Silva FA, Goncalves J. Chimeric Small Antibody Fragments as Strategy to Deliver Therapeutic Payloads. Adv Protein Chem Struct Biol 2018; 112: 143-182.

Cunha-Santos C, Figueira TN, Oliveira SS, Borrego P, Rocha C, Couto A, Cantante C, Santos-Costa Q, Pereira J, Fontes CMGA, Taveira N, Aires-da-Silva F, Castanho MARB, Veiga AS, Gonçalves J. Development of Synthetic Light-Chain Single-Domain Antibodies as Novel and Potent HIV Fusion Inhibitors. AIDS 2016; 30: 1691-1701.

Machado D, Pires D, Perdigão J, Couto I, Portugal I, Martins M, et al. Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity against Drug Resistant Mycobacterium tuberculosis. PLoS ONE 2016; 11: e0149326.

Gigante AM, Hampton CH, Dillard RS, Gil F, Catalão MJ, Moniz-Pereira J, Wright ER, Pimentel M. The Ms6 Mycolyl-Arabinogalactan Esterase LysB is Essential for an Efficient Mycobacteriophage-Induced Lysis. Viruses 2017; 9: E343

Group Members

PhD Students

  • Inês Iria
  • Rita Ribeiro
  • Pedro Fontes
  • Tatiana Arriaga
  • Luciana Pardini

Master Students

  • Ana Margarida Manuel
  • Jéssica Nereu

Trainees

  • Carlos Araújo
  • Miguel Cardoso