Bertram Lab research
About Professor John Bertram
Meet Count Bertram, a nobleman among kidney researchers
Once dubbed 'the Count' because he loves counting, what Professor John Bertram and his team count has made Monash a world leader in kidney research. They tally tiny kidney parts, whose number, fixed before birth, can influence our chances of getting kidney and other chronic diseases as adults.
John began counting nephrons and glomeruli about 20 years ago, when few others were, even though the numbers of these basic kidney-filtering units had been identified as likely indicators of high blood pressure, kidney damage and other chronic diseases as we mature.
His trailblazing work, in conjunction with Australian and overseas researchers, has made Monash the world leader in quantitative kidney pathology - the careful measurement of kidneys and their essential components.
"We've analysed 10 times more human kidney samples than any other group in the world," he says. "We've analysed more than 400 kidneys collected from Australia and around the world and sent to Monash for analysis."
Glomeruli are tiny spherical filtration units in the kidney that filter the blood. They're part of larger structures called nephrons. Together, glomeruli and nephrons help regulate the balance of salts and water and acids and bases, such as urine and blood, in our bodies. They also make vital hormones.
John and his team's painstaking, gold-standard counting methods have confirmed that the traditional estimate of an average one million glomeruli per human kidney was about right but masked a huge variation among people, who could have as few as 200,000 or two million or more.
The variation is significant because a low glomerular count is seen as a major risk factor for high blood pressure, which can lead to stroke, cardiovascular disease, kidney disease and other serious health issues. Just as significantly, our count is fixed for life in our first 36 weeks in the womb.
"If you're born with a low number, that's it," John says. "It's believed that no more are made after a term birth."
Armed with this knowledge, John has tried to work out why some people are born with less glomeruli than others and if we can improve the chances of having a high count at birth.
His work has the potential to save millions of dollars now spent on managing the explosion of high blood pressure and related diseases in adults, especially kidney disease, which has reached epidemic proportions in many groups around the world, including Australia's aboriginal community.
Over the past decade, John's team and national and international collaborators have analysed almost 1000 kidney tissue samples, collected through biopsies, from Aborigines and whites in neighbouring communities in northern Australia.
The Indigenous sample had 20 per cent fewer glomeruli and much more kidney disease.
His team has also examined kidney tissues from white and black Americans in Mississippi and Africans in Dakar, Senegal, from where many black Mississippians' ancestors came as slaves.
The results of all these studies suggest that environmental as well as genetic factors can influence glomerular numbers as the kidney develops in the womb.
John's research was the first to show that low birth weight and overuse of alcohol, and even antibiotics, can lead to a low glomerular count at birth.
With the help of a National Health and Medical Research Council grant, his group is now applying their counting skills to podocytes - tiny octopus-shaped cells that form part of the critically important glomerular filtration barrier.
For decades, podocytes were considered incapable of dividing and, therefore, being replaced if injured. But glomerular stem cells have recently been identified that seem capable of replacing podocytes.
Knowing the numbers of podocytes and stem cells, and how known kidney-disease risk factors alter their number, will provide new insights into the causes and possible treatments of many debilitating conditions, John says.
John is bursting to start using Monash's new magnetic resonance imaging (MRI) unit, due to operate from February 2012, which will give him a full three-dimensional view of a kidney, the progress of disease and the response to new treatments in the same subject over time.
"I want to be in there on day one, and start doing what we've been doing - the world standard, for which we're internationally known - five times faster," he says. "We'll be able to do bigger, smarter and more experiments, which have never been done before because of the time and cost."
Podocyte number and disease
Podocytes are key components of the glomerular filtration barrier. Podocyte loss and injury are key steps that lead to glomerular damage and loss in many forms of kidney disease. Podocytes have little, if any, capacity to be replaced making podocyte protection clinically important. In collaboration with Monash scientists and clinicians and clinicians at the Jikei School of Medicine (Dr Nobou Tsuboi) in Tokyo, we are assessing podocyte number and size in various disease states (mouse, human), and exploring if and how low podocyte number is associated with increased disease risk or reduced response to therapy. (funding from NHMRC and Jikei Medical School).
Ex vivo and in vivo imaging of glomeruli
Low nephron number is often associated with increased blood pressure and increased risk of developing kidney disease. To date, all methods for estimating nephron number have required access to either kidney biopsies or whole kidneys obtained at autopsy. In collaboration with Monash researchers (Monash Biomedical Imaging) and Dr Kevin Bennett and his colleagues at Washington University (St Louis) we are developing magnetic resonance imaging methods for imaging, counting and sizing all glomeruli in the kidneys of mice, rats and sheep. These important studies will enable new and powerful studies of renal development, physiology and pathology, and provide the foundations necessary for imaging and quantitation of glomeruli in patients with kidney disease and those at risk of developing kidney disease (eg. children born small and/or premature). (funding from Monash University).
The super-nephron kidney
Many perturbations to the feto-maternal environment result in offspring with low nephron endowment. In mammals, this nephron deficit is permanent, and is often associated with increased risk of high blood pressure and kidney disease in later life. We have identified a maternal diet that leads to offspring having more nephrons than normal. We are defining: (1) the components of this diet that increase nephron endowment; (2) the cellular and molecular events responsible for this increased nephron number; (3) whether such kidneys are resistant (at least partially) or possibly susceptible to adult stressors such as diabetes and hypertension; (4) and whether this diet can be used to rescue nephron endowment in offspring otherwise destined to develop kidneys with low nephron endowment.
Peritubular capillaries (funding from Australian Research Council)
Visit Professor Bertram's Monash research profile to see a full listing of current projects.
Our studies of kidney development and regeneration utilise a wide range of molecular, physiological and morphological techniques. These include cell and tissue culture (including culture of whole embryonic mouse and rat kidneys, culture of specific subcompartments of developing kidneys, culture of specific cell lines), fluorescence-activated cell sorting (FACS), laser capture microdissection, manual microdissection, imaging [including phase, DIC, fluorescence, confocal microscopy, image analysis, stereology, time-lapse movies and optical projection tomography (OPT)], whole mount and section in situ hybridisation histochemistry, RT-PCR, real time PCR, Northern and Southern blotting, gene microarrays and bioinformatics. Physiological parameters under investigation include blood pressure (tail cuff and telemetry methods), glomerular filtration rate, renal blood flow, and urinary protein.
Many of our studies utilise transgenic reporter mouse strains, or knockout mice. Hoxb7/GFP transgenic mice are an important tool in our research. These mice express GFP (Green Fluorescent Protein) in the ureteric epithelial 'tree', which we can visualise using fluorescent or confocal microscopes. Using a specially designed environmental chamber we can culture Hoxb7/GFP kidneys on a confocal microscope which enables us to image the same kidney on multiple occasions. We can then create time-lapse 'movies' and study growth rates and remodelling of the ureteric tree under different culture conditions.
Our developmental programming studies involve studying the effects of varying maternal diets or treatments on offspring health. Female mice/rats are fed varying diets during pregnancy and the early postnatal period (during lactation). Offspring can be studied as embryos, newborn pups up to adult time-points.
Mr Richard Young and Professor John Bertram, Department of Anatomy and Developmental Biology, Monash University, Monash BDI.)
We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).
We collaborate with researchers from:
- the Departments of Physiology (Monash) and Chemistry (Monash), and Nephrology (Monash Health)
- the University of Queensland
- Washington University (St Louis, USA)
- Aachen University (Germany)
- the University of Heidelberg (Germany)
- the Universitätsklinikum Hamburg-Eppendorf Germany)
- Jikei University in Tokyo, Japan.
Our group has a strong national and international reputation, publishing in excess of 280 original articles, review articles and book chapters.
Student research projects
The Bertram Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short-term research opportunities available. You are encouraged to contact Professor John Betram regarding potential projects that align with the presented research themes.