The smell of success: outstanding newly qualified scientists scoop fellowships

Is it possible to predict how a smell will smell? The answer to this intriguing question could not only help in the manufacture of new perfumes, but could ultimately lead to better drug design, according to Jennifer Brookes, a researcher at University College London.

Jennifer, a physics graduate, is one of 16 newly qualified postdoctoral researchers to receive a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust. During her Fellowship, she will spend time at the Massachusetts Institute of Technology (MIT) in the USA, where development is underway of a ’RealNose’ biosensor for detecting smells.

Odour detection involves small molecules activating much larger protein receptors, setting off a cascade that ultimately activates a region of the brain known as the olfactory bulb. The mechanism by which these molecules interact with the protein receptors is not clear. Only certain molecules can activate a particular receptor; this originally led scientists to suggest a ’lock and key’ analogy. Jennifer argues that this model is flawed.

“We can have one molecule that smells like a lemon, but another structurally very similar molecule that smells completely different,” she says. “To complicate things further, there may be another molecule very different in structure that also smells like a lemon. The lock and key analogy doesn’t work here.”

An alternative theory to explain the mechanism for activation is the ’vibration theory of olfaction’, first proposed in 1937 by Malcolm Dyson and expanded further in 1996 by Luca Turin. All molecules have a natural frequency of vibration, and they argued that it was this vibration that activates the protein receptor. Rather than being analogous to a lock and key, this mechanism has been likened to a ’swipe card’.

Jennifer aims to test the theory at MIT using the RealNose biosensor, which is being developed using real human olfactory receptors. Unlike previous ’electronic noses’, which have been developed to detect specific odours only, RealNose should be capable of identifying novel odours. She hopes that this will enable her to develop a mathematical model that can predict how a particular molecule will smell and also how to develop a molecule that smells a particular way. The applications could be far-reaching, she believes.

“It’s not just about allowing perfumists to design new scents,” she says. “We have a similar situation in drug design. A particular drug target, for example, may behave one way, but changing the direction of just one chemical bond could drastically change how the drug works. Being able to predict which protein receptors a particular drug will act on, and how it acts on it, could help us design more effective drugs.”

The Sir Henry Wellcome Postdoctoral Fellowships provide £250 000 over four years so that researchers can pursue important biomedical research questions, working in the best laboratories in the UK and overseas.

“These awards aim to support a new generation of research leaders,” says Dr Candy Hassall, who oversees the Fellowship programme at the Wellcome Trust. “The Fellowships provide unprecedented freedom at a very early stage, enabling these outstanding newly qualified researchers to choose where they should go to develop their work and their ideas.”

This year’s recipients also include:

Thomas Bowden, Wellcome Trust Centre for Human Genetics, University of Oxford
Using techniques in structural biology, immunology and cell biology, Thomas will study in atomic detail the mechanism by which Rift Valley fever virus and Crimean-Congo haemorrhagic fever virus attach to and infect human cells. Despite the threat that these mosquito- and tick-borne viruses pose, little is currently known about how they infect their host. It is hoped that the information derived from Thomas’s work will ultimately aid in our ability to combat these pathogens.

Oliver Davis, King’s College London
Oliver aims to develop new tools to bring the diverse data from complex genetic studies together into an understanding of the origins of learning disabilities such as dyslexia, behavioural problems such as attention deficit hyperactivity disorder, and developmental difficulties such as autism. He will apply these tools to data from thousands of children in the Twins Early Development Study to unravel the nature and nurture of some of the key problems of childhood.

Marcia Lagarde, University of Sussex
Marcia will study how specific supporting cells within the mammalian inner ear contribute to hearing capabilities. She will examine how the structures of these supporting cells contribute to the excitation of the auditory sensory cells, which they surround, during postnatal development of the cochlea. Excitation of the auditory sensory cells is the first, crucial step in the neural pathway that enables us to hear.

Hannah Mischo, London Research Institute, Cancer Research UK
Human diseases that do not originate from external factors are often caused by mutations in genes encoding proteins that have an essential function for the survival of a single cell, and consequently the entire body. One such essential function is to prevent DNA damage. If genes that code for proteins that guard the integrity of DNA are mutated, cells will accumulate more DNA damage as they age, leading to their premature death. Using a yeast analogy, Hannah will investigate the function of a particular protein that prevents DNA damage accumulation.

Marie Schroeder, University of Oxford
Marie will use a new technique known as ’hyperpolarised magnetic resonance’ to examine in real time cardiac function and energy metabolism throughout progressive heart failure. This approach may help to identify whether disordered metabolism is a cause or symptom of heart failure. She will also examine how patterns of gene expression regulate energy production in the heart and affect whole-heart function. Such information will aid the understanding and diagnosis of heart failure, and will also help to target treatment methods.

Notes for editors

The full list of recipients is:

Erie Boorman, University of Oxford
Dissecting the contribution of anterior prefrontal cortex to decision making with computational, statistical, and neuroimaging approaches.

Thomas Bowden, Wellcome Trust Centre for Human Genetics, University of Oxford
Molecular and functional basis for bunyaviral attachment and fusion.

Jennifer Brookes, University College London
A proposal for the determination of small molecule messages: the enigma of signalling in olfaction.

Jenna Cash, Queen Mary, University of London
Defining the role of chemerin peptides and ChemR23 in the endogenous anti-inflammatory network.

Oliver Davis, King’s College London
Identifying patterns of genome-wide association in the development of cognitive, behavioural and psychiatric disorders.

Paul Huang, Institute of Cancer Research
Development of mass spectrometry tools to study signalling networks in vivo.

Marcia Lagarde, University of Sussex
Roles of the supporting cells in the mechanical responses and neural excitation in the mammalian cochlea.

Andrew Lin, University of Oxford
Stochastic resonance in olfactory sensory processing.

Ivan Matic, Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee
Systems biology profiling of SUMO substrate proteome in signalling pathway.

Lynsey Meikle, University of Edinburgh
The functional implications of Tsc1 loss in visual cortex plasticity.

Hannah Mischo, London Research Institute, Cancer Research UK
SEN1 implications in DNA damage: an insight into AOAII.

Sophie Pinner, University College London
Regulation of dendritic cell motility within stromal niches of lymph nodes.

Jasmina Saric, Imperial College London
Differential metabolic mapping of immune mechanisms: The Leishmania major induced TH paradigm in a new context.

Marie Schroeder, University of Oxford
Assessment of in vivo metabolism in failing hearts using hyperpolarised carbon-13 magnetic resonance.

Bernhard Staresina, University of Cambridge
Functional integration in the human medial temporal lobe during episodic memory encoding and retrieval.

Mary Wu, MRC National Institute for Medical Research
Identifying components of a halting mechanism that controls delamination during epithelial-mesenchymal transition

About the Wellcome Trust
The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.