Principal Supervisor: Dr. Aparna RatheeshLink opens in a new window

Co-supervisor: Dr. Mohan Balasubramanian

PhD project title: Macrophage functions during repair and organogenesis

University of Registration: University of Warwick

Project outline:

Macrophages are highly migratory immune cells capable of engulfing and removing dead cells, debris and pathogens. Macrophages, also known as hemocytes constitute 95% of the immune cell population in Drosophila Melanogaster, are highly migratory and bear striking similarities to their mammalian counterparts in migratory behaviour, function and ontogeny¹ making it an excellent model system to understand embryonic macrophage migration. Sterile injuries in Drosophila embryos result in hemocyte recruitment to wounds in a process which is highly similar to vertebrate inflammatory response and are involved in phagocytosis and removal of apoptotic cells. Hemocytes also secrete a large repertoire of extracellular matrix proteins such as Collagen and Laminin which are essential during embryogenesis. Thus hemocytes are integral during embryogenesis and essential during adult life similar to vertebrate macrophages. Our lab is currently interested in understanding the contribution of hemocytes to organogenesis as well as repair and regeneration using interdisciplinary approaches integrating cell biology, genetics, biophysics and cutting-edge microscopy. Vertebrate macrophages are known to be highly effective at performing different and sometimes even opposing functions depending on the context; an example is the pro and anti-tumor functions exhibited by macrophages. We believe that understanding how Drosophila hemocytes respond to different physiological and pathological conditions would enable us to better understand and devise better intervention strategies to counter or enhance vertebrate macrophage functions during disease.

This project will study the mechanistic details of how macrophages are recruited to specific sites and work to understand the hierarchy and kinetics of macrophage functions at these sites. We will aim to answer these overarching aims through these specific objectives:

1. Understand the biophysical and biochemical cues that drive macrophage recruitment to developing organs and sites of repair. 2. Decipher the functional differences exhibited by hemocytes in diverse environments such as developing kidneys and sites of wounding and repair.

Methods: Drosophila genetics, optogenetics, live imaging of embryos using a confocal and two photon microscope, FACS sorting, ex vivo migration assays, biophysical manipulations, quantitative image analysis and mathematical modelling.

Reference:

1. Ratheesh A, et al. Curr Opin Cell Biol. 2015;36:71
   
   

BBSRC Strategic Research Priority: Understanding the rules of life – Immunology, and Integrated Understanding of Health - Regenerative Biology.

 

Techniques that will be undertaken during the project:

Drosophila genetics

Optogenetics

RNA interference technology and CRISPR/Cas9

Two-photon and Dual Inverted Selective Plane Illumination Microscopy (diSPIM)

Laser Ablation

Cell culture techniques

Migration and confinement assays

FACS sorting

Quantitative image analysis

 

Contact: Dr. Aparna RatheeshLink opens in a new window