Ben Warren

Royal Society University Research Fellow

Although there are no current vacancies I am constantly applying for research funding so 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.

Research Interests

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.

Research 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 sound-induced deafness 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 whole-cell patch-clamp recordings in auditory neurons of the locust to understand the basis of these early changes that lead to eventual deafness.

3. Understanding the fundamental basis of concussion

Concussion is not unique to humans. In fact if you take any nervous system and accelerate it fast enough it will temporarily stop working. In my lab we exploit the high throughput (and relatively ethical) approach of using insects to better understand concussion. Concussion, at its fundamental level, is the inactivation of our neural cells and although we have some clues to the mechanisms contributing to our neural system 'shut down' there is no rigorous quantitative measure of their relative contribution. For this project we use a range of insects to 1) see if the mechanism of concussion are similar across a wide range of animals 2) quantify, for the first time, the fundamental neuronal basis of concussion.

Methods/Techniques

    • Whole-cell patch-clamp
    • 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

Publications

Warren B and Göpfert M C Proprioceptive responses from the pentascolopidial chordotonal organ of Drosophila larvae. In preparation for Journal of Experimental Biology.

Warren B, Georgina E Fenton, James FC Windmill, Elizabeth Klenschi, Andrew S French Physiological basis of noise-induced hearing loss in a tympanal ear. BioRxiv (due to be submitted to eLIFE). https://www.biorxiv.org/content/10.1101/698670v1

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  https://www.ncbi.nlm.nih.gov/pubmed/29540551

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. https://www.ncbi.nlm.nih.gov/pubmed/27476597

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. https://www.ncbi.nlm.nih.gov/pubmed/26823514

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. https://www.ncbi.nlm.nih.gov/pubmed/25950634

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. https://www.ncbi.nlm.nih.gov/pubmed/25253851

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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871864/

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.

Impact

Mechanotransduction in stretch-sensitive neurons
Synaptic connectivity in the antennal lobe
Auditory basis of mating in mosquitoes

Keywords

 

Mechanotransduction
Mechanotransduction ion channel
Patch-clamp
Noise-induced hearing loss
Temporary hearing loss
Concussion

 

Collaborators

James Windmill
Tom Matheson
Martin Göpfert
Marta Andres
Peter Kloppenburg

Memberships and other responsibilities

I am the University of Leicester representative for the Physiological Society https://www.physoc.org/
I am currently the vice president for the Post Doc and Research Staff Association for the College of Life Sciences https://www2.le.ac.uk/colleges/medbiopsych/internal/res/post-doc-research-staff-association

Teaching Skills/Experience

Sensory Neuroscience
Lab practicals

Locust ear holder 3D print design

Here is the file to print off a Locust ear holder described in my latest paper.

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.

Public Engagement at the Brain Awareness Day

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)

Ben Warren

Location

Adrian Building 304

Contact information

t: 0116 252 5366 
e: bw120@le.ac.uk

Other non-research Output

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