Here is a fairly random collection of
stuff from my career. Right at the start, I would like to thank
all my supervisors, colleagues and collaborators for their help
and support over the years, especially Hugh Miller and
colleagues in the Miller group at the University of Edinburgh
vet school. My career to date in scientific research has spanned
from 1984 to 2012, during which time I worked at University of
Edinburgh Chemistry Department, Moredun Research Institute and
then the Royal (Dick) School of Veterinary Studies. My final
year of employment was spent working in the new Roslin Institute
building at Easter Bush. Circumstances forced me to take early
retirement at the end of Jan 2012, but I would gladly take up
the test tubes again if the right offer came along.
Most of the projects I've worked on have
run their course and been summarised in published papers, so
there's no need to go into details here. But in addition to
that, I have come up with various "off the wall" scientific
hypotheses that developed as side-lines, and I would dearly have
loved the opportunity to follow them up. However, for the
meantime, the best I can do is to get them down in writing here,
and perhaps they might be picked up and carried forwards in some
way by others. Please note that these are simply hypotheses and
not accepted facts, and quite possibly they could be completely
wrong. I will gladly remove any of the following ideas if anyone
can show me that they are wrong or misleading.
Research ideas
On the composition of mucus - read more here...
Summary: Gastrointestinal (GI) mucus is composed of a mixture of
the products (predominantly mucins, water and ions) secreted
from the epithelial layer, along with the remains of exfoliated
epithelial cells and a certain amount of transudated plasma.
This hypothesis states that in addition to secreted products,
exfoliated epithelial cells and transudated plasma are essential
components of GI mucus and that variations in mucus properties
between different regions of the GI tract and in disease may be
explained by a combination of changes in the rate of epithelial
secretion, exfoliation of epithelial cells and transudation of
plasma. Or to look at it another way, the reason for the rapid
turnover of epithelial cells in the GI tract (complete
replacement in approx 4 days) is because they are required to
form a functional mucus barrier.
Extracellular histones and
cardiovascular disease
Summary: We and others have shown that histones are capable of
aggregating lipoproteins. We have also shown that histones
effectively form crosslinks between lipoproteins and
proteoglycans. Additionally, it has been recently shown that
severe inflammation causes the buildup of toxic levels of
histones in the circulation. In this hypothesis, I speculate
that chronic inflammation causes an increase in circulating
histones at a sub-clinical level, that supports a gradual
increase in the deposition of lipoproteins on arterial wall
proteoglycans. This may play a role in the known association
between chronic inflammation of all kinds and increased risk of
cardoivascular disease. You can read more about this idea in the
PLoS One paper that I wrote with Jeremy Brown here.
On the inverse relationship between
circulating intelectin (omentin) and cardiovascular disease
risk
Summary: Intelectin-1 (Itln1; also known as omentin-1) is a
protein that is expressed in the secretory goblet cells of most
mammals. We have shown that its expression in these cells can be
highly up-regulated by the presence of even very low
concentrations of Th2 cytokines IL-4 and IL-13 (these are
signalling molecules that are typically found at elevated levels
during parasitic infections). In humans, intelectin-1 is also
produced by endothelial cells (which make up the lining of blood
vessels) as well as stromal vascular cells within omental fat (a
type of abdominal fat). The latter cell types produce high
levels of Itln1, which is detectable in blood plasma. Many
different studies have consistently shown that the level of
Itln1 in plasma can be inversely linked with the risk of type 2
diabetes or cardiovasular disease. In this hypothesis, I suggest
that the pro-inflammatory state of abdominal fat in obesity is
linked to a reduction in the level of IL-4 / IL-13 expression in
obese omental tissue and consequently a reduction in the output
of Itln1 by omental cells. If correct, this would mean that
plasma Itln1 represents a highly sensitive marker for the
inflammatory status of omental adipose tissue. It would be
interesting to explore the effect of culturing omental stromal
vascular cells in the presence of Th2 cytokines.
Publications
Peer reviewed papers
There are 60-odd publications to list, so I am grateful to the people / servers at BiomedExperts for doing all the hard work of compiling the list, which can be viewed here. Registration is required to see the full list.
Unpublished information
Some research has proved hard to get published, which has been frustrating. It will make me feel better to get this information out into the public domain, for what it's worth. It may just be of interest to one or two researchers out there!
Posters
MODELLING GOBLET CELL RESPONSES IN ALLERGY
AND PARASITISM
Jeremy K. Brown, Steven H. Wright, Julie A. Bethune, Pamela A.
Knight and Alan D. Pemberton
Presented at the Easter Bush Research Consortium launch event, Edinburgh International Conference Centre, 7-8 April 2008. This poster summarises data that we tried several times to publish without success.
Download the pdf here: (615 Kb)
Retracted papers
Identification of agarose and
ribonucleotide-binding properties of human intelectin-1
Alan D. Pemberton, Valerie I. Rae, Erin D. T. Manson
Submitted in this form to BBRC. Rejected 25 Nov 2011 due to perceived lack of scientific value. More detailed quantitative biochemistry would be required for this reviewer. Unfortunately, I was no longer in a position to carry out this additional work. *** Important: this paper was retracted by ADP on 27 August 2021 due to the realisation of a misinterpretation of the data. ***
To read the retracted paper, click here.
(C) Alan Pemberton, last edited 27/08/21