Life Sciences Research for Lifelong Health

Michael Coleman

Michael Coleman is now Professor of Neuroscience in the Department of Clinical Neuroscience, University of Cambridge. He remains an Affiliate Scientist at the Babraham Institute.

Research Summary

We study basic mechanisms regulating axon survival. Age-related axon loss contributes to declining memory, senses, autonomic nervous system (bladder, gut, etc.) and motor function, leading to physical frailty. It also sets the biological context for age-related neurodegenerative disease.
We identified a protein that delays degeneration of injured axons, or Wallerian degeneration, by tenfold. We investigate its mechanism and the pathway on which it acts, including signalling by pyridine nucleotides and a Toll-like receptor adapter. In line with BBSRC’s strategic priority ‘Healthy Ageing across the Lifecourse’, we study the contribution of this mechanism to age-related axon loss.

For example, we find that axonal transport of NMNAT2 is essential for axon survival but this transport declines during normal ageing. Consequently, we are testing whether depleting NMNAT accelerates age-related axon loss and whether blocking the pathway delays it.  
In knowledge exchange activities with Alzheimer’s Research UK, the Motor Neuron Disease Association and Takeda Cambridge Ltd, we also study axons in age-related disease. We investigate dystrophic axons in Alzheimer’s disease, modifiers of axon loss in amyotrophic lateral sclerosis and axonal transport in peripheral neuropathy.
In summary, our primary aim is to understand processes within axons that enable these remarkable cellular structures up to one metre long to survive for over 80 years. In parallel, we maximise the exchange of knowledge, skills and resources with research into age-related diseases. Understanding normal ageing is essential for a full understanding of age-related neurodegeneration.


Motor axon detail

Motor axons in humans are up to a meter long. In mice they are over 5 cm.
The figure shows the first few hundred microns (approximately half a millimeter) of a motor axon in a mouse.
The vulnerability of these structures to any blockage of axonal transport is immediately apparent.   


Group Members

Latest Publications

Reduced number of axonal mitochondria and tau hypophosphorylation in mouse P301L tau knockin neurons.

Rodríguez-Martín T, Pooler AM, Lau DH

Neurobiology of disease
85 1095-953X:1-10 (2015)

PMID: 26459111

Short-term diabetic hyperglycemia suppresses celiac ganglia neurotransmission, thereby impairing sympathetically mediated glucagon responses.

Mundinger TO, Cooper E, Coleman MP

American journal of physiology. Endocrinology and metabolism
309 1522-1555:E246-55 (2015)

PMID: 26037249

Absence of SARM1 rescues development and survival of NMNAT2-deficient axons.

Gilley J, Orsomando G, Nascimento-Ferreira I

Cell reports
10 2211-1247:1974-81 (2015)

PMID: 25818290

Axonal transport declines with age in two distinct phases separated by a period of relative stability.

Milde S, Adalbert R, Elaman MH

Neurobiology of aging
1558-1497: (2014)

PMID: 25443288

The Axon-Protective WLD(S) Protein Partially Rescues Mitochondrial Respiration and Glycolysis After Axonal Injury.

Godzik K, Coleman MP

Journal of molecular neuroscience : MN
1559-1166: (2014)

PMID: 25352062

A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration.

Di Stefano M, Nascimento-Ferreira I, Orsomando G

Cell death and differentiation
1476-5403: (2014)

PMID: 25323584

Age-related axonal swellings precede other neuropathological hallmarks in a knock-in mouse model of Huntington's disease.

Marangoni M, Adalbert R, Janeckova L

Neurobiology of aging
35 1558-1497:2382-93 (2014)

PMID: 24906892