Dr Massimiliano Baldassarre
Eukaryotic evolution has been shaped by the billions of years of continuous interaction with bacteria and other microorganisms. Either to use them as food or being used and parasitized by them.
Therefore, studying how cell and organism (the host) interact with bacteria and other microorganism is a powerful method to shed light on fundamental cell biology mechanisms and at the same time a fundamental tool to reveal mechanisms used by microbes to colonise and survive in the host.
In addition to answer basic Cell Biology questions, the study of host-microbe interactions addresses important human health-related issues such as for example:
How immune cells recognise and eliminate pathogen?
How immune cells communicate each other to coordinate the organism response to the infection?
How bacteria become pathogens and why some restrict their infection to specific host?
The research in our lab is aimed to answer those and other important host-microbes interactions related questions.
more info on our external website:
Why Salmonella enterica serovar Typhi infect only humans?
One central question that we are addressing is about the host mechanisms restricting Salmonella Typhi from infecting non-susceptible hosts.
Salmonella Typhi is an exclusive human pathogen and the cause of typhoid fever, a life-threatening systemic disease that affects millions of people and kills more than 200,000 every year. The goal of our research is to gain insights into the molecular and cellular mechanisms of Salmonella Typhi pathogenesis and its human-adaptation. We use an advanced cell biological approach, where imaging and biochemical analyses are integrated by genetic, genomic and proteomic methods. These studies are also intended to address fundamental questions in the cell biology of the host.
We recently discovered a novel host-defence mechanism that protects against Salmonella Typhi infections. We showed that Salmonella Typhi clearance ex vivo in macrophages, and in vivo in mice, depends on an intracellular trafficking pathway regulated by the Rab GTPase Rab32 and its guanine nucleotide exchange factor (GEF) BLOC3 (BLOC-3 and Rab32 dependent Anti-Microbial, BRAM pathway).
We are actively studying this pathway and aiming to answer the following questions:
- How is the Rab32-dependent trafficking pathway regulated?
- Is the Rab32-dependent trafficking pathway active in human macrophages? If so, how does Salmonella Typhi evade killing and replicate in human macrophages?
- What killing molecules does the BRAM pathway deliver to the bacterial containing vacuole?
- Is it possible to stimulate it and "boost" innate immunity mechanisms?
(Prof Stefania Spano)
Prof Daniel Kümmel (University of Münster, Münster, DE)
Prof Gordon Dougan (University of Cambridge, UK)
Prof Alexander Westermann (University of of Würzburg, DE)
Prof Lars Barsquit (University of of Würzburg, DE)
Prof Matteo Zanda (CNR - Consiglio Nazionale delle Ricerche Milan Italy)
Prof David A. Calderwood (Yale University, New Haven, CT, US)
Prof Iain McEwan (University of Aberdeen)
Dr Subhankar Mukhopadhyay (King's College London)
Funding and Grants
Targeting Filamin-androgen receptor interaction could represent a novel strategy for prostate cancer treatment.
4th year BM4004/BM4010 Advanced Molecules, Membranes and Cells University of Aberdeen; lectures:
- Cell-ECM interaction 1
- Cell-ECM interaction 2
4th year MB4050 The Dynamic Cell University of Aberdeen; lectures:
- Introduction to Cytoskeleton 1
- Introduction to Cytoskeleton 2
- Cell Adhesion
- Cell Migration
- Workshop: Honours project Skills Workshop
3rd year 3503 The Molecular Control of Cell Function University of Aberdeen; lectures:
- Cell-ECM interaction 1
- Cell-ECM interaction 2
- Cell-Cell interaction 1
- Cell-Cell interaction 2
3rd year 3006 Molecular Biology of the Cell University of Aberdeen; lectures:
- Cell architecture 1
- Cell architecture 2
- Cell architecture 3
- Workshop: Cell Architecture
2nd year BI25M5: Microbes , Infection and Immunity
- Practical: Identification & Growth of Pathogens
1st year SM1501 The Cell
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A Small-Scale shRNA Screen in Primary Mouse Macrophages Identifies a Role for the Rab GTPase Rab1b in Controlling Salmonella Typhi GrowthFrontiers in cellular and infection microbiology, vol. 11, 660689Contributions to Journals: Articles
Bscl2 Deficiency Does Not Directly Impair the Innate Immune Response in a Murine Model of Generalized LipodystrophyJournal of Clinical Medicine, vol. 10, no. 3, 441Contributions to Journals: Articles
The Rab32/BLOC-3–dependent pathway mediates host defense against different pathogens in human macrophagesScience Advances, vol. 7, no. 3, eabb1795Contributions to Journals: Articles
VARP and Rab9 Are Dispensable for the Rab32/BLOC-3 Dependent Salmonella KillingFrontiers in cellular and infection microbiology, vol. 10, 581024Contributions to Journals: Articles
Design, synthesis, conjugation and reactivity of novel trans,trans-1,5-cyclooctadiene-derived bioorthogonal linkersBioconjugate Chemistry, vol. 31, no. 9, pp. 2201-2210Contributions to Journals: Articles
Structural basis of the filamin A actin-binding domain interaction with F-actinNature Structural & Molecular Biology, vol. 25, pp. 918-927Contributions to Journals: Articles
Novel Synthetic Strategies for the Development of Tryptophan-Proline Chimeras, Useful Tool for Drug DiscoveryCurrent Bioactive Compounds, vol. 12, no. 3, pp. 161-167Contributions to Journals: Articles
Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-β-dependent mechanismsPNAS, vol. 113, no. 31, pp. E4558-4566Contributions to Journals: Articles
NGR Tumor-Homing Peptides: Structural Requirements for Effective APN (CD13) TargetingBioconjugate Chemistry, vol. 27, no. 5, pp. 1332-1340Contributions to Journals: Articles
ASB2α, an E3 ubiquitin ligase specificity subunit, regulates cell spreading and triggers proteasomal degradation of filamins by targeting the filamin calponin homology 1 domainThe Journal of Biological Chemistry, vol. 288, no. 44, pp. 32093-32105Contributions to Journals: Articles