Unfolding the Future - The Functional Fold: Amyloid Structures in Nature - page 160

there was the first report of functional amyloid identified within
the human body as a structure to template melanin (Chapter 9).

In 2007, the first systematic study of amyloid distribution

6

in

vivo revealed an unexpected abundance of amyloid in bacterial

communities.

7

With a jump in the number of reports of functional
amyloid in the past few years,

8-10

the topic is developing into an
exciting new multidisciplinary field with broad implications for
our understanding of protein function, the evolution of natural
materials and the underlying cause of amyloid-based diseases. As
the field expands, the many functional attributes of the amyloid fold
are expected to be employed beyond their natural manifestation in
novel applications. In this final chapter we explore some of these
emerging aspects of functional amyloid as well as summarizing the
current challenges in the development of the field.

10.2 The Challenge of Identification

Many of the discoveries of functional amyloid to date have occurred
via serendipity in scientific research, often in laboratories that had
other, initially unrelated projects on pathogenic amyloid, or staff
with prior experience in the pathogenic amyloid field. It is thus
highly plausible that amyloid occurs far more commonly in nature
than is currently apparent, but has remained unidentified. This may
primarily be due to continuing problems with definitive identification
of amyloid and the difficulties associated with analysing the
composition of highly insoluble amyloid fibrils. Currently, there are
a broad range of techniques that are used to suggest the presence
of amyloid including Thioflavin T fluorescence, Congo red binding,
luminescent conjugated polyelectrolyte probes, circular dichroism
spectroscopy, Raman spectroscopy, and Fourier transform infrared
spectroscopy, fibril observation in electron microscopy or atomic
force microscopy images, X-ray fibre diffraction and the use of
amyloid specific antibodies. However, no single technique is accepted
in isolation as providing a definitive identification of amyloid due
to the large number of false positives that can occur and the often
highly specific requirements of the sample preparation not to incur
a false negative. As a consequence the onus is on the researcher to
obtain as many positive indications of amyloid as is possible for a
particular sample using a number of the available techniques. This