THE UK SEMIOCHEMISTRY NETWORK CHEMICAL SIGNALS IN VERTEBRATES, BRITISH WORKSHOP XXIII ______

Gonville and Caius College, Cambridge.

21 - 22 July 2015

An informal one-and-a-half day workshop on “The Sense of Smell” in man and other vertebrates.

WORKSHOP PROGRAMME

...... Day One Noon – 12.55pm Registration.

1:00pm Lunch

2:20pm Welcome and Introduction

2.25pm Linking physiology to perception in the olfactory system chaired by Johan Lundström Karolinska Institutet, Stockholm & Monell Chemical Senses Center, Philadelphia

During the last decade, we have witnessed a great leap forward in our understanding of how the olfactory system creates the final odor percept. In this symposium, four speakers will provide overviews of the current knowledge of how each processing step (the sniff, the odor receptors, the olfactory bulb, and the cortex) contributes to our everyday odor experience.

2:30pm Reading minds through the nose: the sniff as experimental and diagnostic tool – Anat Arzi, Weizmann Institute of Science, Rehovot.

Sniffing, the active process of olfactory information acquisition through sampling of volatile molecules, is an integral part of olfactory perception. Sniffing modulates olfactory perception, and in turn, odor properties such as intensity and pleasantness modulate sniffing. Thus, the sniff offers a unique nonverbal measure of olfactory perception. Specifically, the nonverbal nature of the olfactory sniff response, in which pleasant odors drive stronger sniffs and unpleasant odors drive weaker sniffs, provides an experimental and diagnostic tool. In my talk, I will discuss the interaction between sniffing and smelling and will elaborate on the use of the sniff as an experimental tool for sub-threshold odor detection, and odor processing in the absence of olfactory awareness in health and disease.

3:00pm The role of a single odorant receptor in human perception – Joel Mainland, Monell Chemical Senses Center, Philadelphia

In color vision, genetic variation in a single type of color receptor leads to red-green colorblindness. Humans also have genetic variation in odorant receptors, suggesting that there may be olfactory phenomena analogous to color blindness. Current models, however, do not predict how the absence of a single odorant receptor will alter olfactory perception. Taking advantage of the large amount of genetic variation in the human population, we have begun to identify perceptual correlates. Building on this genetic model, we have also used in vitro screening to identify receptor antagonists, allowing us to reversibly inhibit OR activity and probe the effects on odor perception. By understanding how variation in a single receptor alters the perceptual code, we hope to build a more comprehensive model of odor coding.

3:30pm The olfactory bulb and beyond: Cortical contributions to olfaction – Donald Wilson, NYU, New York

The olfactory bulb receives direct input from olfactory sensory neurons in the nose and plays an important role in representing the molecular features of inhaled odors. Local olfactory bulb circuits enhance contrast between similar features and thus serve to help separate overlapping input patterns to improve discrimination. Despite these basic sensory functions, olfactory bulb processing is highly dynamic, shaped by both past-experience and current behavioral state. This presentation will review recent work exploring dynamic odor processing in the olfactory bulb.

4:00pm Tea Break

4:30pm Cortical mechanisms of odor object formation –Janina Seubert Karolinska Institutet, Stockholm

Our understanding of peripheral and early cortical olfactory processing has benefitted greatly from insights based on analogous systems in non-primates. By contrast, the extensive cortical network subserving olfactory processing in human is unique to our species, and its role in shaping our odor experiences is only beginning to be explored in depth. This presentation will highlight recent advances made in the understanding of higher-order cortical olfactory processing. A particular focus will hereby be placed on adaptive functions of the cortical olfactory network during the integration of olfactory inputs with their larger cognitive, emotional and sensory context.

The Dave Kelly Lecture

5:00pm Does it matter when the sense of smell is lost? - Thomas Hummel, Smell & Taste Clinic, Dept of ORL, TU Dresden, Germany

Smell loss is frequent. In the general population 5-20 % exhibit complete or partial loss of olfactory function which is especially frequent with aging. However, relatively little is known – even among non-clinical olfactory researchers – about the various causes of olfactory loss, the possibility of spontaneous recovery from smell loss, or specific forms of treatment in relation to the origin of the disorder. The presentation will also focus on the question whether human olfaction is really of importance considering the large number of people without a functioning sense of smell.

Perfumery Presentation

6.00pm You see-smell it or you don’t, that is the question – Christophe Laudamiel, DreamAir

6:30pm Break

7:30pm Workshop Dinner

Day Two

9:00am Clinical session chaired by Carl Phillpott, University of East Anglia, Norwich.

9:05am Managing parosmia and phantosmia – Antje Welge-Lussen, University Hospital Basel, Switzerland.

Parosmia and phantosmia are qualitative olfactory disorders which are yet difficult to measure. Nevertheless they often go along with quantitative disorders which can be measured but which are sometimes slight in cases of a predominant qualitative disorder. This talk covers clinical workup in quantitative disorders and gives an overview regarding discussed pathophysiology. In consideration of this treatment options as far as they exist and prognosis are discussed as well.

9:35am Coping with a lost sense – Tom Laughton, Fifth Sense.

This is a personal account of the emotional impact of smell loss. Following an assault 25 years ago, Tom has had a very limited sense of taste and smell. In this talk he will open up how he has tried to interpret what the loss has meant, how it has affected his feelings of engagement in his life and surroundings, and how he has adapted to these losses.

10:05am Smell diaries - using memory to manage anosmia – Lisha McLelland, Queen Elizabeth Medical Centre, Birmingham

10:35am Understanding The ‘Gatekeeper’: Disgust - Lorenzo Stafford, University of Portsmouth

Recent theories on the emotion of Disgust propose it can be separated into three different domains (pathogen, sexual, moral), each having a distinct adaptive function. However, the extent to which moral disgust relates to these other more visceral forms is unclear. Using a novel olfactory paradigm, we present data that examines this question.

10:45am Tea Break (Including AGM).

11:15am Psychology session chaired by John Behan, University of Kent, Canterbury.

11:20am Memory reactivation during Sleep by Odors – Julia Rihm, University Medical Centre, Hamburg-Eppendorf and Bjorn Rasch, University of Fribourg, Switzerland.

Memories are consolidated during sleep. One method to examine such sleep-dependent memory consolidation is to tag items during encoding with a background odor. The olfactory cue alone is then re-presented during subsequent sleep. This “targeted memory reactivation” triggers item memory consolidation during sleep. I will present a set of studies where we investigated the effect of olfactory targeted memory reactivation in different memory domains, and by this means substantiate the causal role of sleep in declarative and emotional memory consolidation.

11:50am Effect of insulin on the Sense of Smell, Memory and Taste – Jessica Freiherr, Uniklinik RWTH, Aachen, Germany.

The hormone insulin is considered an important key signal between the endocrine system and the brain, especially during the regulation of food consumption. We hypothesize that the anorexigenic effects of insulin are mediated by a modulation of the processing of chemosensory signals. With this set of studies we aim to examine the effects of an increased cerebrospinal insulin level on chemosensory perception as well as memory processes. Our results provide innovative insights into the interaction of cerebrospinal insulin with the chemosensory systems. Conclusions on the fundamental mechanisms of insulin effects on food consumption and the mediation of satiety in healthy subjects can be drawn.

12:20pm Effect of fragrance use on discrimination of individual body odor – Caroline Allen, University of Stirling

Research suggests that rather than masking individuals’ odour, preferred fragrances may actually complement, and potentially enhance, idiosyncratic differences in human body odour. Based on this assumption it can be predicted that discrimination of odours would be improved when odours were paired with a fragrance of choice as opposed to an allocated fragrance, and the current study aimed to test this hypothesis.

12:30am ABCC11 – The key human anti-odor target – Dorothea Schweiger and Julia Gallinger, Beiersdorf AG, Hamburg, Germany.

The axillary odor of humans is the result of bacterial action on odor precursor molecules that are secreted by apocrine sweat glands. In many Asians, which only exhibit a faint acidic odor, the apical efflux pump ABCC11 is nonfunctional. ABCC11 transports the precursor molecule of the odorous 3-methyl-3-sulfanylhexanol (3M3SH). Therefore, ABCC11 plays a key role in the formation of body odor and provides an interesting target for the development of deodorants.

1:00pm Lunch

2:00pm Mammalian Semiochemistry Session chaired by Darren Logan, Wellcome Trust Sanger Institute, Cambridge.

2:05pm Exploiting human odours for the control of biting insects – James Logan - London School of Hygiene & Tropical Medicine

2:35pm Molecular biomarkers of neurodegenerative disease in the olfactory epithelium – Gabriela Sanchez-Andrade, Wellcome Trust Sanger Institute

Olfactory dysfunction is one of the earliest and most prevalent symptoms of neurodegenerative disorders (ND). Here I present an olfactory transcriptomic analysis of a mouse model of Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). We find that, from ~17,000 genes expressed in the olfactory epithelium (OE), over 2,000 genes were differentially expressed between mutants and control animals. We established a reduced repertoire of genes, the “Cambridge Set”, to study based on the propensity of their protein product to aggregate in ND. We show the Cambridge Set can distinguish FTDP-17 mice from a range of healthy controls. These experiments suggest that analysis of just 35 genes expressed in the OE may indicate the early stages of neurodegenerative disease. I’ll additionally present our progress into applying this approach to humans.

3:05pm Odor blockade of innate aversion – Luis Saraiva, EMBL-EBI & Wellcome Trust Sanger Institute

How odors elicit pleasing or disagreeable sensations is unknown. Surprisingly, we found that ligands for the same olfactory receptor can stimulate different mouse behaviors and, furthermore, that attractive and aversive odorants can block one another's effects. Moreover, ablation of a single receptor can eliminate the odor blockade. The behavioral effect of an odorant is therefore context-dependent and can be profoundly influenced by interactions among signals downstream of different receptors.

Closing remarks and end of meeting

Delegates

Caroline Allen University of Stirling, UK [email protected] Anat Arzi Weizmann Institute of Science, Israel [email protected] Benjamin Auffarth [email protected] John Behan University of Kent, Canterbury and Sensorii, Ashford, Kent [email protected] Duncan Boak Fifth Sense [email protected] Carles Bosch The Francis Crick Institute - Mill Hill Laboratory, London [email protected] Christine Cahen Proctor & Gamble, Belgium [email protected] Craig Chisholm IFF, Haverhill, Suffolk [email protected] Wouter De Weirdt Tectero Bvba [email protected] Roger Duprey Duprey Definessence Design Ltd. [email protected] Jessica Freiherr Uniklinik RWTH Aachen, Germany [email protected] Julia Gallinger Beiersdorf AG, Hamburg, Germany [email protected] Simon Gane UCL [email protected] Matthew Grub Kings College, London [email protected] Andrew Horsfield [email protected] Thomas Hummel Smell & Taste Clinic, Dept of ORL, TU Dresden [email protected] Ximena Ibarra-Soria Wellcome Trust Sanger Institute [email protected] Jo Jacobius Axiom Communications [email protected] Chris Kelly Fifth Sense [email protected] Christophe Laudamiel DreamAir LLC, New York [email protected]

Tom Laughton Fifth Sense [email protected] Darren Logan Wellcome Trust Sanger Institute [email protected] James Logan London School of Hygiene & Tropical Medicine [email protected] Johan Lundström Karolinska Institutet, Stockholm & Monell Center, Philadelphia [email protected] Joel Mainland Monell Chemical Senses Center, Philadelphia [email protected] Bob Margolskee Monell Chemical Senses Center, Philadelphia [email protected] Lisha McLelland Queen Elizabeth Medical Centre, Birmingham [email protected] Javier Medina Proctor & Gamble, Belgium [email protected] Carsten Muller Cardiff School of Biosciences, [email protected] Simon O’Connor Biocomputation Group, University of Hertfordshire [email protected] Carl Philpott School of Medicine, University of East Anglia, Norwich [email protected] Julia Rihm University Medical Center Hamburg-Eppendorf, Germany [email protected] Carmen Rueda Hernandez The Fat Duck, Bray [email protected] Gabriela Sanchez-Andrade Wellcome Trust Sanger Institute [email protected] Luis Saraiva EMBL-EBI & Wellcome Trust Sanger Institute [email protected] Glenis K. Scadding RNTNE Hospital, London [email protected] Janina Seubert Karolinska Institutet, Stockholm [email protected] Lorenzo Stafford Department of Psychology, University of Portsmouth [email protected] John Stephen Cotswold Perfumery [email protected] Antje Welge-Lussen University Hospital, Basel, Switzerland [email protected] Simone Weyand [email protected] Donald Wilson NYU, New York [email protected] Tristram Wyatt [email protected]