Dr Benjamin Warren

Opportunity for German Researchers to visit my lab for 6-24 months

As a previous Alexander von Humboldt recipient I can host Feodor Lynen Postdoctoral Fellows. If you live in Germany and are interested in working on any aspect of mechanotransduction or sensory transduction in insects (flies, locusts, mosquitoes etc...) using techniques (electrophysiology, bioinformatics, metabolics, genomics, behaviour), and want to experience the diverse pleasures of Leicester please get in contact to let me know where your interests lie and we can start to draw up a strategic application.

Other opportunities to work in my lab

I am always keen to hear from eager Post Graduate Students, Post Docs and Technicians who wish to work in my growing lab. I especially encourage those wishing to apply for Early Career Fellowships to get in contact as I will provide extensive help with the application process.

My fascination with sensory neuroscience was forged during my observations of swarming mosquitoes during my undergraduate degree. The female mosquito’s high-pitched whine (all too familiar to victims of their bites) turns out to be necessary for male mosquitoes to locate them. The remarkable auditory sensitivity of mosquitoes is underpinned by ~16,000 neurons, jam-packed into a tiny structure the size of a pin-head. My imagination was captured by these mechanosensory neurons and sparked a question which has guided my research journey ever since: How do insect auditory neurons convert sound-induced nanometre displacements into electrical signals that the insect can hear?

To pursue this question I migrated to the renowned Kloppenburg lab in Cologne to learn the art of patch-clamping: a powerful electrophysiological tool for understanding the inner electrical workings of neurons. I gained further experience in the world-famous Göpfert lab in Göttingen which utilised the fruit fly to understand the molecular basis of mechanotransduction.

Studies of auditory neurons in insects were hampered by a lack of electrical recordings of the fundamental mechanical-to-electrical step. To address this gap in knowledge I turned to the locust, which has large accessible auditory neurons, which I brought the powerful patch-clamp technique to bear. In the thriving neuroscience community at Leicester, and within the specialist Locust Labs (headed by Drs Tom Matheson and Swidbert Ott), I pioneered the first patch-clamp recordings from insect (locust) auditory neurons. I now use the locust ear as a model system to understand basic principles of auditory transduction that apply across animals.

Projects

1. Identification and characterisation of the auditory mechanotransduction ion channel in the ear of the desert locust
   
   The identity of the elusive auditory mechanotransduction ion channel remains outstanding for any animal ear, including our own, despite a three-decade search to find it. Why, then, has the locust ear entered the race to find the channel? My current work in this area stands on the shoulders of the Drosophila giants, which have narrowed down candidate proteins thought to be the auditory transduction ion channel. My established patch-clamp recordings build on this body of work by measuring the current flowing directly through the mechanotransduction ion channel itself. I use a pharmacological and biophysical approach to shed light on the channel’s identity and characterise its biophysical properties. I am currently developing CRISPR-Cas9 genetic editing to knockout candidate mechanotransduction ion channel genes.


2. Characterisation of the physiological basis of noise-induced and age-related hearing loss in insect auditory neurons
   
   At first glance it seems far-fetched to use locust ears to understand deafness across animals – including humans. At the fundamental level however, all ears attempt to do the same thing: sensitively convert sound waves into neural potentials that we can hear. Bearing this in mind it is no surprise that invertebrates and vertebrates alike have come to common solutions to detect sound; for instance the same ‘gating-spring’ model can explain auditory transduction in vertebrate hair cells and antennal sound-receivers of insects. In addition, there is considerable conservation of the genes that specify the development of ears, so much so that these ear-specifying genes can be swapped between mice and flies! Whatever the auditory system, excessive deafening-sound leads to the excessive inflow of current into auditory neurons through the mechanotransduction ion channels. This, in turn, activates other ion channels and triggers downstream processes which lead to a decrease in the ability of the auditory neurons to transduce sound. The work in my lab uses a variety of electrophysiological, bioinformatical and molecular biological techniques to understand the basis of these early changes that lead to eventual deafness.

Blockley A, Ogle D, Warren B Physiological changes in the ear due to age and noise - a longitudinal study (Under review in iScience)

Warren B, Georgina E Fenton, James FC Windmill, Elizabeth Klenschi, Andrew S French Physiological basis of noise-induced hearing loss in a tympanal ear. Journal of Neuroscience (2020) Vol. 40L 3130-3140. DOI: 10.1523/JNEUROSCI.2279-19.2019

Warren B and Matheson The role of the candidate mechanotransduction ion channel Nanchung-Inactive in auditory transduction in an insect ear. Journal of Neuroscience, 2018, Vol. 38, 3741-3752. DOI: 10.1523/JNEUROSCI.2310-17.2018

Andrés M, Seifert M, Splathoff C, Warren B, Weiss L, Giraldo D, Winkler M, Pauls S, Göpfert M C. Auditory efferent system modulates mosquito hearing. Current Biology, 2016 ,Vol. 26 1-9. DOI: 10.1016/j.cub.2016.05.077.

Rotte C, Warren B, Bardos V, Schliecher S, Klein A, Kloppenburg P. Ca2+ dependent K+ currents in uniglomerular olfactory projection Neurons. Journal of Neurophysiology Vol, 115, 2330-2340, 2015.

Alexandre N, Spalthoff C, Kandasamy R, KatanaR, Rankl N B, Andrés M, Jähde P, Dorsch J A, Stam L F, Braun F-J, Warren B, Salgado V L, Göpfert M C. TRP channels in insect stretch-receptors as insecticide targets. Neuron Vol. 86, 1-7, 2015.

Warren B, Kloppenburg P. Rapid and slow chemical synaptic interactions of cholinergic projection neurons and GABAergic local interneurons in the insect antennal lobe. Journal of Neuroscience Vol. 24, 13039-13046, 2014.

Warren B, D Fusca, Kloppenburg P. Chemical intracellular signalling in the antennal lobe of the cockroach Periplaneta Americana. 13th EuropeanSymposium on Insect Olfaction and Taste, Villasimius, Cagliari, Italy, 2013.

Warren B, Russell I J. Mosquitoes on the wing 'tune in' to acoustic distortion. Progress in auditory Biomechanics, p.479-480, 2011.

Warren B, Lukashkin A N, Russell I J. The dynein-tubulin powers active oscillations and amplification in the hearing organ of the mosquito. Proceedings of the Royal Society B Biological Sciences Vol. 277, p.1761-1769, 2010.

Gibson G, Warren B, Russell I J. Humming in tune: sex and species recognition by mosquitoes on the wing. Journal of the Association for Research in Otolaryngology Vol. 11, p.527-540, 2010.

Pennetier C, Warren B, Dabire R, Russell I J, Gibson G. Singing on the wing as a mechanism for species recognition in the malarial mosquito Anopheles gambiae. Current Biology Vol. 20, Issue 2, p.131-136, 2009.

Warren B, Gibson G, Russell I J. Sex Recognition through Midflight Mating Duets in Culex Mosquitoes Is Mediated by Acoustic Distortion. Current Biology Vol. 19, p.485-491, 2009.

Open access to my datasets

Please find data for my publications below:

• Blockley et al., 2021:
• Laser data (Fig. 2)
• Hook electrode data (Fig. 3)
• Muller's organ anatomical data (Fig. 4)
• Patch-clamp data (Fig. 5)

Current Lab members

• Tom Austin (PhD Student)
• Christian Thomas (Post Doc)

Warren Lab Alumni

• Daisy Ogle (Post Doc)
• Now student recruitment and outreach officer at Leicester


• Georgina Fenton (Post Doc)
• Now Post Doc at Universitat CEASAR, Bonn, Germany


• Alix Blockley (Post Doc)
• Now Lecturer at University of Leicester


• Ben Cooper (Post Doc)
• Now data scientist intern at University of Leeds

• Whole-cell patch-clamp
• Two-electrode voltage-clamp
• Matabolic assays
• Confocal imaging and neuronal staining
• Extracellular on-cell and nerve recordings from chordotonal organ stretch-sensitive neurons
• RNA extraction, cDNA synthesis, PCR, Gel Electrophoresis, RACE
• CRISPR-Cas9 and RNAi (in development)
• Interferometer and Doppler laser recordings of insect sound-receivers

How to get an Early Career Fellowship

I have been lucky enough to be a recipient of three Early Career Fellowships so I have written some advice on How to Get an Early Career Fellowship. I have also made a short powerpoint presentation including How to go from being a postdoc to getting a research fellowship – in 7 steps, with a Star Trek the Next Generation theme! Please contact me if you would like copies of successful applications to: the Alexander von Humboldt Postdoctoral Research Fellowship, Leverhulme Trust Early Career Fellowship and Royal Society University Research Fellowship.

How to build a super-stable custom microscope for Patch-clamp recordings for £13.5k (ex VAT)

If you are an eager 'Patcher' wanting to build your own setup but have a limited budget you're not alone. I have constructed a super-stable microscope for patching with finely-controlled piezo-driven motors on each of the three axis. The components (mostly from Thor Labs) are listed below:

• Cerna Mini Microscope (SFM2), £7,180.39
• Condenser Holder (BSA2000), £545.27
• Condenser (CSC2001), £992.66
• Objective (Nikon CFI Apochormat NIR 40X W, Supplier Nikon), £1,552
• LED Driver (LEDD1B), £235.60
• Power Supply for LED Driver (KPS101), £25.75
• Infrared LED (M780L3), £170.20 *Infrared cuts really well through tissue to give you a clear image* *I have used some elastic bands to attach it directly underneath the condenser*
• Right Angle Clamp for 66 mm Rail (XT66RA1), £39.00 *To connect 66 mm rail on which condenser holder is bolted to the Cerna Microscope main body*
• Construction rail (XT66-100), £27.19 *The condenser holder needs to be cut and then bolted onto this rail*
• CCD Camera Jenoptik Proges Gryphax SUBRA Camera, £2,850 (Supplier Indigo Scientific)

• Alexander von Humboldt Research Fellowship
• Leverhulme Trust Early Career Fellowship
• Royal Society University Research Fellowship (current)

I am co-organising Invertebrate Sound and Vibration at Lincoln 30 March – 2 April 2023