The Gould lab public engagement web site
The idea behind these pages is to provide the public with access to our research, and to explain what we do, why we do it, who pays for it and so on.
Follow the links below for some of the answers.
If you would like more information, or would like to give us some feedback on this web site (good or bad), please e-mail Gwyn Gould.
What is basic research?
“Basic research (or fundamental research) is research carried out to increase understanding of fundamental principles. Many times the end results have no direct or immediate commercial benefits: pure research can be thought of as arising out of curiosity. However, in the long term it is the basis for many commercial products and applied research. Pure research is mainly carried out by universities.” (Wikipedia).
Work in the Gould lab seeks to advance understanding in and knowledge of aspects of cell biology. In this regard, our group attempts to generate hypotheses about the behavior of cells, then design experiments to refute or support them. In this regard, we try to understand how a cell works, how it operates, in a normal situation. In the sections which follow, we provide some examples of this work in a format we hope is understandable to the layperson.
Here's another Wikipedia quote:
“Pure research generates new ideas, principles and theories, which may not be immediately utilized.......though are the foundations of modern progress and development in different fields. Today's computers could not exist without the pure research in mathematics conducted over a century ago, for which there was no known practical application at that time. Pure research rarely helps practitioners directly with their everyday concerns. Nevertheless, it stimulates new ways of thinking about deviance that have the potential to revolutionize and dramatically improve how practitioners deal with a problem.”
There are numerous examples of this in biology, such as the application of the polymerase chain reaction (PCR) technique in modern forensic science and its use in the diagnosis and understanding of the genetics of diseases (key advances here came from studies of bugs that grow in hot springs) or the use of monoclonal antibodies to treat cancer (e.g. Herceptin). It is important to realize that basic science can build new knowledge, the application of which can often not be foreseen (sometimes called ‘blue-skies research’).
Most of us work in areas of biology which are in some way relevant to disease processes. Even though, like the Gould lab, scientists may not directly study disease cells or samples, the argument is that only by understanding how a cell is supposed to work can we design a rational therapy for the treatment of disease.
Our lab works in an area of science called Cell Biology, a discipline that studies cells – how they behave, their structure, the organelles (compartments) within them, how they move, how they change in the cell cycle and so on. We use arrange of approaches from microscopy to genetic manipulation of cells in culture to ask questions about basic cellular processes. We believe that understanding these basic processes will inform the basic sciences of cell and molecular biology, and have future applications in biomedicine and biotechnology in the years ahead.
How does basic science work?
Anatomy of scientific career!
This cartoon is clearly stylized, but has some elements of truth. Starting from ‘an idea’ (seldom arrived at in a “eureka moment”, usually ideas are based upon reading the work of others and steady progress in a given field), the first objective is to persuade someone to pay for your experiments. So, we enter the grant writing phase. This is characterized by hours of reading, word-processing, form-filling and fretting, until your grant is submitted to a funding agency (see "who pays for it.").
The funding agency will have many dozens of applications, so they invite experts to read your grant and comment on it, often making suggestions and criticisms which you need to answer before a decision on your grant application is made. Based upon the (anonymous) comments of the expert reviewers a panel of your peers will decide which 10% (or so) of the submitted grants will get funded. (Success rates range from between 5% to 15% at present, depending on the organization).
Funding levels vary, but for our group we typically request funding in three year cycles, supporting a postdoctoral worker (see "who does the experiments") and covering the costs of doing the experiments, buying the equipment, etc.
The plan is that the postdoc does the experiments then you assemble the data into a cogent story and try to publish it. Here, one is faced with the vagaries of scientific research - things don't always go quite the way we predict (time to refine that hypothesis!), but with luck after a while, through your skills and intellect, you will have developed credible answers to a particular conundrum, and will attempt to publish your results.
Here, one is again at the mercy of anonymous referees. We assemble our work into what we think is a sensible and cogent analysis and ask a journal to publish it. They will ask several independent experts to referee your work. If you can satisfy any questions these referees’ raise, then the journal will publish your results. Fame and glory will follow….perhaps.
[As one would expect, there is a hierarchy amongst journals (dictated by the so-called h-index). The h-index is an index that attempts to measure both the productivity and impact of the published work of a scientist. The index is based on the set of the scientist's most cited papers and the number of citations that they have received in other people's publications.]
Who does the experiments?
In most University laboratories the majority of the work is performed by postgraduate students (studying for either a Masters degree or a Doctorate (PhD)), or by postdoctoral researchers – these are young scientists who have completed a PhD and are undertaking a period of further training. In the Gould lab, these individuals are supported by a superb technician, Clare.
Jennifer Rocissana with visiting student Paul Purvis
Where do we do them?
We work in the Davidson Building on the green and pleasant Gilmorehill campus of the University of Glasgow. Our laboratory space is shared with other research groups (including that of our long-standing collaborator, Dr Nia J. Bryant – you can view her web pages here). It is a large lab, designed to hold up to 40 scientists in one large space. The idea of such an ‘open-plan’ lab is to foster interactions between the scientists (often, throw away remarks over a coffee or across the bench can have a profound impact on experiments) and so encourage students and postdocs to think ‘outside the box’. It is too easy to get overly focused on one approach to solve a problem. Sometimes, a fresh eye or a different approach can pay dividends. We believe that this open-plan lab goes a long way towards encouraging this attitude. And, in these financially uncertain times, it is a more cost-effective way to run a group.
Our lab was refurbished by a large grant (£2.3million) from the Wellcome Trust Joint Infrastructure Fund in 2000, led by Gwyn Gould, which provided money to re-design and equip the space, including an array of key facilitating equipment. A photo of the lab is below.
Who pays for it and what does it cost?
Research in the Gould lab is supported by Cancer Research UK, Diabetes UK, Diabetes Research and Wellness Foundation, and the Biotechnology and Biological Sciences Research Council (BBSRC). Links to the websites of these agencies are provided.
To pay the salary of a postdoctoral worker and pay for the expensive reagents we need to do the experiments, charities such as Cancer Research UK and Diabetes UK provide funds which average at around £60,000 to £80,000 per scientist per year.
Expensive equipment such as the confocal microscope shown above costs around £250,000. The confocal shown above was provided by funds from the BBSRC.
Our over-arching theme: How do Cells Compartmentalize?
Let’s first begin with some basics about cells. Cells are the basic building blocks from which complex creatures (like ourselves, plants or animals) are made. An adult human is made up of about 100,000,000,000,000 (100 trillion) cells, the vast majority of which are small, of the order of 0.00001m across.
White blood cells
We study mammalian cells. A key defining feature of mammalian cells (indeed of all eukaryotes) is that they contain membrane-bound compartments within which specific cellular functions take place. These include the nucleus (which contains the cell’s DNA) and the mitochondria (which are regarded as the energy factories of the cell). All cells contain many distinct intracellular compartments, some of which can be seen on the high magnification electron microscopy image shown (left), and in cartoon form (right).
|Image from www.lookfordiagnosis.com||www.ibri.org|
So, why do cells compartmentalize? Well, compartmentalization allows the cell to specialize certain biological activities in one small space, making the processes involved more efficient. So, it makes sense to have many of the energy-producing processes in one compartment (mitochondria), the cells destructive machinery used to ‘chew up’ unwanted material in another (lysosomes), and so on. This does, however, pose the cell with the requirement for a mechanism to allow different membrane-bound compartments to communicate. This process is referred to as ‘membrane trafficking’. Understanding the mechanism and regulation of membrane trafficking is the overarching objective of the Gould lab.
In order to move something (we call this ‘cargo’ – its red spots in this figure) from one compartment (donor) to another (target compartment), mechanisms have evolved to allow the cargo to be packaged into small membrane ‘vesicles’ which bud-off the donor compartment, move to the acceptor compartment, and then fuse with it. A bit like this:
Processes like this occur between all of the membrane compartments inside our cells, and the itinerary gets very complex:
In this figure, red arrows are showing routes of ‘forward traffic’. Here, new protein cargo is made in the endoplasmic reticulum, processed in the Golgi apparatus and then sorted into its subsequent destination. Sometimes, proteins are moved ‘back’ towards the ER or Golgi (we call this retrograde traffic – it’s shown here as blue arrows). Regardless of the role of these different pathways, they all share the same basic mechanism of trafficking shown in the cartoon above.
When this trafficking machinery goes wrong, the consequence for the cells can be bad. One can imagine that defects may arise if the wrong cargo is selected, the vesicles don’t bud off from the donor properly, cannot reach their destination, or arrive at the wrong destination. There are numerous examples of diseases which are characterized by defective membrane trafficking – providing a clear example of the importance then of asking basic questions. We contend that only by understanding how cells are supposed to function can we rationally design therapies to combat malfunctions in disease.
Some examples of funded research projects and progress to date
Cancer Research UK funded work.