Dr Ann Rajnicek

Prizes and Awards

Yasuda Award for Excellence in Biomedical Research (Jan 2000) Society for Physical Regulation in Biology and Medicine.

Research Overview

I am interested in the process by which cells use environmental conditions as guidance cues during development, wound healing and regeneration. My work has potential applications in tissue engineering and for devising clinical strategies to aid wound healing and nervous system repair. 

Guiding cells by DC electric fields

Cells exist within a naturally-occuring electric field, which results from the normal ion transport properties of polarized epithelia.  My research addresses the question of how cells use the electric field as a cue to direct cell migration and orientation.

Guiding cells by small substratum contours

The physical shape of the extracellular environment is usually not considered in the context of directional cell migration.  However, cells migrate along parallel substratum features on the scale of tens to hundreds of nanometers, which mimic the size of naturally ocurring features (such as individual collagen fibrils or oriented neuronal fibers).  I am interested in the process by which individual cells sense very small substratum features and how they translate the cues subsequently into directed migration.

Establishing a guidance heirarchy

Since electric fields and variation in substratum shape co-exist in vivo another interest is to determine the hierarchy of directional cues and the mechanisms that allow the cues to be selected/integrated by individual cells.  

Rho GTPases and growth cone guidance by an electric field

The Rho GTPases Rac, Rho and Cdc42 regulate cytoskeletal dynamics spatially and therefore control cell shape and the direction of cell migration.  We have shown that Rho GTPase-mediated cytoskeletal dynamics are essential for growth cone guidance by an electric field (Rajnicek et al., 2006 Journal of Cell Science 119:1723-1735;  Rajnicek et al. 2006 Journal of Cell Science 119: 1736-45). 

Current Research

 Growth cone guidance by substratum grooves

Growth cones are exquititely sensitive to substratum features on the scale of tens of nanometers deep but not all types of growth cones respond in the same way to identical features.  For example, embryonic rat hippocampal axons align at a right angle to a series of parallel grooves 130 nm deep and 1 um across but Xenopus spinal neuron growth cones migrate parallel to the same grooves.  I  am currently exploring the intracellular mechanisms growth cones use to detect small substratum features, including roles for Rho GTPases and the transcription factor Pax-6 (collaboration with Martin Collinson and Derryck Shewan, School of Medical Sciences, University of Aberdeen).

Guidance of epithelial cells by substratum nanotopograpy and electric fields is controlled by a rho/cdc42 switch 

Cells migrating to re-epithelialise a wound in the cornea migrate over non-planar surfaces within the context of a wound-induced DC electric field.  We have shown that corneal epithelial cells migrate parallel to nano-scale substratum grooves and that on planar quartz they migrate toward the cathode of a DC electric field.  By simultaneously challenging corneal cells with co-presented substratum grooves and an electric field oriented orthogonally we determined that the electric field was a more potent directional cue and that a cdc42/rho switch controls electrical/contact guidance priority.  This is relevant to the design of future therapies to aid wound healing as well as the basic mechanism for how cells sort/select/integrate simultaneous directonal guidance cues present in the normal extracellular environment.

Collaborations

Aberdeen- Prof Nieves Casan-Pastor, Dr W Huang, Dr D Shewan, Dr M Collinson, Dr H Wilson, Prof M Delibegovic 

Funding and Grants

IMS Spinal Research Fund -PhD Studentship "Electrical Control of Nerve Cell Growth"

School of Medical Sciences -PhD Studentship "The transcription factor Pax6 and neuronal guidance" (with M Collinson and D Shewan)

European Commission Specific Targeted Research or Innovation Project - "Development of a Bioelectrochemical device for CNS repair" (NERBIOS)  ~£220,000 (with C.D. McCaig)

BBSRC - Genetic control of epithelial cell migration and wound healing physiology (with M Collinson, C McCaig and M.Zhao) ~£643,000.

Teaching Responsibilities

Course Coordinator:

AN4301- Developmental Neuroscience with Anatomy

PY4302- Developmental Neuroscience

AN4002/AN4003- Brain Function and Malfunction

BM3804- Neuroscience Research Topics

Non-course Teaching Responsibilities

Senior Personal Tutor for School of Medicine, Medical Sciences and Nutrition (undergraduates)

Personal Tutor and related pastoral care for undergraduates

Industrial Placement Tutor

Chair Level 2 undergraduate Staff Student Liaison Committee