Using nanobodies to cross the blood brain barrier for drug delivery

Using nanobodies to cross the blood brain barrier for drug delivery

Project details

Developing potent therapeutics against brain cancers and neurodegenerative diseases is hampered by the difficulties for drugs to cross the Blood Brain Barrier (BBB), a formidable barrier that protects the brain from toxins and pathogens. Transferrin receptor (TfR1) naturally crosses the BBB to provide the brain with iron using a process called receptor-mediated transcytosis. Intriguingly, TfR1 is a known attachment site for some of the deadliest infectious diseases caused by malaria and New World Hemorrhagic Arenaviruses. This project focuses on identifying nanobodies that bind to TfR1 to allow transport across the BBB, generating a scaffold for delivering drugs to the brain for treatment of a wide range of diseases.

Skills learnt: Protein expression and purification, nanobody characterization, biochemical assays (FRET, BLI), structural biology techniques (X-ray crystallography, cryo-electron microscopy)

About our research group

The Tham lab has made fundamental discoveries in understanding the molecular and structural mechanisms that drive host-pathogen interactions, guiding rational design of new therapies against infectious diseases. Recently, we have been developing therapeutics against malaria and SARS-CoV-2 using nanobodies and human antibodies. 

This project combines our fascination with infectious diseases and therapeutic drug development to uncover novel ways to deliver drugs across the blood brain barrier. Using our in-depth understanding of Transferrin receptor/pathogen interactions and leveraging off exciting collaborations with chemists and cell biologists, we will deliver targeted drugs to a difficult to treat part of the human body. 

References

Gruszczyk, Nature 2018 559(7712):135-139; Gruszczyk, Science 2018 359(6371):48-55; Chan, Nat Commun. 2021 12(1):1538; Pymm and Adair, PNAS 2021 118(19) e2101918118) 

 

 

Email supervisors

 

Researchers:

Dr Gabby Watson profile picture
Dr
Gabby
Watson
Infectious Diseases and Immune Defence

Project Type: