adp-stuff: science

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)

Peer-reviewed 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.

To read the paper, click here.

adp-stuff

(C) Alan Pemberton, last edited 28/04/12