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Dr Rachel McMullan

Professional biography

I completed my PhD in Biosciences at The University of Birmingham in 2003, studying the role of Rho small GTPases in keratinocyte function. Following this I undertook a postdoc at the MRC Laboratory for Molecular Cell Biology investigating the function of Rho family small GTPases during neurotransmitter release in Caenorhabditis elegans.

In 2010 I became a Wellcome Trust Career Development Fellow at Imperial College using C. elegans to study the relationships between the nervous and immune systems the mediate responses to infection. 

I joined the School of Life, Health and Chemical Sciences in 2015 as a lecturer.

1999 BSc Biochemistry and Molecular Cell Biology The University of Birmingham 

2003 PhD Biosciences The University of Birmingham 

Research interests

Host pathogen interactions

Most organisms have evolved strategies to cope with the presence of pathogens in their environment. Whilst the immune system recognizes and eliminates pathogens, changes in neuronal signaling alter animal behavior to avoid these microbes. Bidirectional communication between the nervous and immune systems can modify responses to infection, and this relationship may explain why psychological stress increases susceptibility to infections. In addition activation of the immune response following infection may influence the nervous system leading to the development of sickness syndrome and depression. Because of the complicated nature of the mammalian brain and immune system the cellular events that underlie neuronal regulation of the immune response remain unclear. 

The nematode worm Caenorhabditis elegans lives in the soil and encounters many pathogens. To survive in these conditions it has evolved conserved immune responses, which can be studied in the lab. C. elegans also has a relatively simple nervous system that shares many common features with the neurons in our own brain. Because of its relative simplicity and the ease with which C. elegans can be manipulated in the lab it has emerged as an excellent model to study how animals recognize pathogens and coordinate neuronal and immune responses to infection. 

C. elegans infected with Microbacterium nematophilum (image by Rachel Ward and Jemima Burden)

Using C. elegans genetics we are studying the ways in which the nervous system regulates the immune response. We have identified a role for the neurotransmitter serotonin in suppressing the immune response and are working to identify other neurotransmitters and neuropeptides that affect immunity.

The ultimate goal of our studies is to understand how these genes influence communication between the nervous and immune systems of mammals, including humans, and to use C. elegans as a tools to screen for drugs that alter these interactions. These could be used to reduce infection susceptibility during stressful situations or to treat neurological disorders that are associated with infection.  

Pathogen avoidance behaviour

Avoidance behaviours are the first line of defence against pathogens and have been selected for throughout evolution; simply put animals that avoid situations where the risk of infectious disease is high are more likely to survive and procreate. The human emotion of disgust is an adaptive disease avoidance system that could be harnessed to prevent infectious disease spread. Since human disgust must share common ancestry with pathogen avoidance behaviours in other animals we can begin to understand disgust through experimental studies of pathogen avoidance in animals. 

The nematode worm Caenorhabditis elegans is routinely used as a genetic model to dissect complex behaviours. We and others have established C. elegans as a cost-effective invertebrate model of pathogen avoidance. This model will provide a platform for further investigations into the evolutionary role of pathogen avoidance behaviours in host defence and the effect of life-traits such as ageing on pathogen avoidance behaviour.  

A full understanding of the evolution of pathogen avoidance behaviours could be used to inform the design of public health interventions that will be important in disease control. Interventions based on emotional drivers of behavior, including disgust, have been used to improve hygiene and handwashing rates in rural India (the SuperAmma trial).

The effect of organophosphate exposure on neuronal function and its role in mood disorders

In collaboration with Dr Gini Harrison (Psychology)

Previous research has reported a link between exposure to organophosphate (OP) pesticides, mood disorders and suicidal behaviour. The mechanism through which OP exposure may result in mood disorders is unclear. Some researchers have suggested that they may also cause changes to serotonergic and dopaminergic pathways, which are systems involved in mood and stress regulation. Using behavioural assays in C. elegans we are studying how the long-term, low level OP exposure that has been associated with mood disorders affects neuronal development and function.

Selected Publications

2014
Anderson A. and McMullan R. From head to tail it's a two way street for neuro-immune communication Worm 3(3) e959425
2013
Anderson A, Laurenson-Schafer H, Partridge F, Hodgkin J, McMullan R. 2013, Serotonergic Chemosensory Neurons Modify the C. elegans Immune Response by Regulating G-protein Signalling in Epithelial Cells, PLOS Pathogens Vol:9(12), e1003787
Anderson A, Kang S, McMullan R, 2013, A simple method for quantifying M. nematophilum clearance from the rectal opening of C. elegans, Worm Breeders Gazette, Vol:19 (4), Pages: 15-16 
Anderson A, McMullan E, 2013, A modified leaving assay to study pathogen avoidance, Worm Breeders Gazette, Vol:19 (4), Pages: 13-14 
2012 
Anderson A, McMullan R, G-proteins: Fighting infection on two fronts, Worm, Vol:1, ISSN:2162-4046, Pages:196-201
McMullan R, Anderson A, Nurrish S, 2012, Behavioral and Immune Responses to Infection Require G alpha q- RhoA Signaling in C. elegans, PLOS Pathogens, Vol:8, ISSN:1553-7366, Pages:e1002530-e1002530

Teaching interests

Currently teaching on the following modules;

SK320 Infectious disease and public health

SDK100 Science and health

S350 Evaluating contemporary science

SDK228 The science of the mind-investigating mental health

Impact and engagement

I am currently a STEM ambassador and Nuffield placement provider

I have recently been a competitor in "I'm a scientist get me out of here" and presented "The Disgust Instinct" with Valerie Curtis (London School of Hygiene and Tropical Medicine) the 2016 Cheltenham Science Festival. 

I am currently organising the Royal Society Evolution of Pathogen and Parasite Avoidance meeting that will take place at Chichley Hall, UK in June 2017 

External collaborations

 Member Genie (Group of elegans new investigators in europe)

Research Activity

Externally funded projects

Genetic analysis of post-developmental Rho GTPase signaling: identification and characterization of Rho signaling pathways required during the C. elegans immune response. (Transfer In)

RoleStart dateEnd dateFunding source
Lead18/May/201531/Jan/2016WELLCOME Wellcome Trust
Rho signaling has been extensively studied using biochemistry and cell-based assays that have demonstrated roles for Rho in many basic cell functions. These studies have told us a lot about the functions of Rho, however little about their importance in a whole animal. Rho signaling is essential during development making it difficult to study Rho’s role in adult animals. Analysis of adult Rho signaling pathways is important because aberrant signaling by these pathways has been implicated in human disease. In this study I aim to define the Rho pathways that act in adult animals. In particular I will identify those pathways that trigger changes in cell morphology as part of the C. elegans innate immune response. By identifying effectors important for this phenotype we will better understand Rho’s role in controlling cell morphology in adult animals. The innate immune system is evolutionarily conserved, for example, both Rho and MAPKinase function in the mammalian immune system and this is also true in C. elegans. In addition cross talk between Rho and MAPKinase pathways has been suggested to contribute to the action of oncogenic Ras. The molecular interactions that mediate this cross talk and Rho’s activation during the immune response remain poorly described and this phenotype provides a genetic model to dissect them. Defining these pathways and the relationships between them in C. elegans is likely to tell us more about how they are involved in innate immunity and misregulated in diseases such as cancer.

Publications

From head to tail it's a 2 way street for neuro-immune communication (2014)
Anderson, A. and Mcmullan, R.
Worm, 3, Article e959425(3)
Serotonergic chemosensory neurons modify the C. elegans immune response by regulating G-protein signaling in epithelial cells (2013-12-12)
Anderson, Alexandra; Laurenson-Schafer, Henry; Partridge, Frederick A.; Hodgkin, Jonathan and McMullan, Rachel
PLoS Pathogens, 9, Article e1003787(12)
G-proteins: fighting infection on two fronts. (2012-10-01)
Anderson, Alexandra and Mcmullan, Rachel
Worm, 1(4) (pp. 196-201)
Behavioral and immune responses to infection require Gαq - RhoA signaling in C. elegans. (2012-02-16)
Mcmullan, Rachel; Anderson, Alexandra and Nurrish, Stephen
PLoS pathogens, 8, Article e1002530(2)
The Pseudomonas aeruginosa reference strain PA14 displays increased virulence due to a mutation in ladS. (2011-12-22)
Mikkelsen, Helga; Mcmullan, Rachel and Filloux, Alain
PloS one, 6, Article e29113(12)
The RHO-1 RhoGTPase modulates fertility and multiple behaviors in adult C. elegans. (2011-02-28)
Mcmullan, Rachel and Nurrish, Stephen J.
PLoS ONE, 6, Article e17265(2)
Rho deep in thought. (2007-11-01)
Mcmullan, Rachel and Nurrish, Stephen J.
Genes & Development, 21(21) (pp. 2677-82)
The Gα12-RGS RhoGEF-RhoA signalling pathway regulates neurotransmitter release in C. elegans (2006-12-13)
Hiley, Emma; Mcmullan, Rachel and Nurrish, Stephen J.
EMBO journal, 25(24) (pp. 5884-5895)
Rho is a presynaptic activator of neurotransmitter release at pre-existing synapses in C. elegans. (2006-01-01)
Mcmullan, Rachel; Hiley, Emma; Morrison, Paul and Nurrish, Stephen J.
Genes & Development, 20(1) (pp. 65-76)
Keratinocyte differentiation is regulated by the Rho and ROCK signaling pathway (2003-12-16)
Mcmullan, Rachel; Lax, Siân; Robertson, Vicki H.; Radford, David J.; Broad, Simon; Watt, Fiona M.; Rowles, Alison; Croft, Daniel R.; Olson, Michael F. and Hotchin, Neil A.
Current Biology, 13(24) (pp. 2185-2189)
A putative C. elegans melatonin receptor is required for efficient pathogen clearance (2016-06-01)
Mcmullan, Rachel; Anderson, Alexandra; Chew, Yee Lian; Taylor-smith, Leanne; Schafer, William and May, Robin
In : European Worm Meeting (EWM 2016) (01-03 June 2016, Berlin ) (p 168)

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