World Health Day: Hope for effectively treating patients with Familial Hypercholesterolaemia (FH).
The death of a 10-year-old boy in the 1990s inspired Professor Derick Raal to dedicate his life to finding a treatment for homozygous Familial Hypercholesterolaemia.
At the time, there was little treatment for the genetic condition that is caused by a defect on chromosome 19, which renders the body unable to remove Low-Density Lipoprotein (LDL) cholesterol from the blood.
The condition causes extremely high levels of LDL cholesterol to build up in a person’s body, clogging the arteries and causing cardiac disease and heart attacks at extremely young ages.
Raal’s dedication to his research, however, resulted in the highly satisfying result of medication that could be used to effectively treat patients with Familial Hypercholesterolaemia (FH).
“It has been a remarkable journey since the 1990s from virtually unable to treat the condition to finding a cure. It does mean that you are on medication for life but you are able to live a normal, healthy life,” explains Raal.
The medication developed from his research was approved by the US Food and Drug Administration in July 2015.
Raal, the Director of the Carbohydrate and Lipid Metabolism Research Unit at Wits specialises in both heterozygous and homozygous FH. Heterozygous FH, the “single dose” is one of the most commonly inherited conditions and affects one in every 250 people worldwide.
In South Africa, the Afrikaner, Indian and Jewish communities are especially affected, with one in every 80 people living with the condition. Homozygous FH, the “double dose” is rare, but is even more serious and is caused when a child inherits the defective genes from both his parents.
Unable to process LDL cholesterol at all, the result is that four times the normal amount of cholesterol builds up in the body.
“Patients with this condition often die of heart attacks as teenagers,” says Raal. “It is devastating to see young people dying from this condition. That is what got me into this field of research.”
Unlike dietary induced high cholesterol, which is caused by a bad lifestyle and can be reduced by a healthy diet and regular exercise, FH in both forms needs to be treated with medication for life.
Raal’s research into finding a treatment for the condition led to the development of a drug called Mipomersen.
The drug cuts cholesterol levels of people living with FH by 30%. His research was published in The Lancet in 2010 and this article has been cited almost 400 times.
“It was quite a breakthrough, but not enough,” says Raal.
He continued his work, which led to the development of PCSK9 inhibitors that can cut cholesterol levels by a further 60%.
His two papers on the use of this medication in heterozygous and homozygous FH were also published in The Lancet in January 2015. “We have basically cured heterozygous FH,” says Raal.
The PCSK9 inhibitors bring cholesterol levels of patients living with heterozygous FH down to normal levels, whilst it brings the cholesterol levels of patients living with homozygous FH down to the levels of those with heterozygous FH. The problem with FH, however, is that it is difficult to diagnose, as sufferers are not aware that they are living with the condition.
“Until one suffers a heart attack or stroke, FH is asymptomatic, so people do not feel sick and do not realise they have the condition,” adds Raal. “With an estimated 200 000 people in South Africa living with FH, the challenge now is to identify these subjects.”
Raal has received numerous awards for his work. He has co-authored over 170 articles and has reviewed for several international journals, including The New England Journal of Medicine, The Lancet, The American Journal of Cardiology, Diabetes Care, Atherosclerosis and Arteriosclerosis, Thrombosis and Vascular Biology.
He is also a member of several scientific societies.
Understanding CLIC proteins
- Wits University
Health Awareness Month: Dr Sadhna Mathura is excavating the hidden potential of chloride intracellular channel (CLIC) proteins in the human body.
Mathura, a Claude Leon Research Fellow at the Protein Structure Function Research Unit (PSFRU) at Wits, says CLIC proteins are commonly associated with vertebrates and found within most of our vital organs such as the heart, brain and muscles.
Most proteins are either soluble or insoluble within a cell.
What makes CLIC proteins different is the fact that under certain conditions they can change their state from soluble to insoluble, enabling them to oscillate between the cytoplasm of a cell and the cell membrane.
“This useful ability has earned these enigmatic compounds the stage-name, the ‘chameleon proteins’,” says Mathura.
Her project focuses on the human CLIC4 protein. The work may have remarkable implications for the treatment of various diseases precipitated by cell death and toxicity, such as cancer, Alzheimer’s and Parkinson’s.
“If we can understand what causes these proteins to undergo these ‘spontaneous’ conformational changes and thus protein unfolding, we may be able to understand the impact it has on these diseases,” explains Mathura.
Her plan of action is to pin down and exploit the precise conditions that facilitate the not-so-spontaneous structural changes of CLIC proteins. Being typically localised in the membrane, certain cellular stress inducers can cause the protein to move into the nucleus.
Recent work has shown that one such stress inducer is the presence of nitric oxide in the cell and this has been implicated in the translocation of CLIC4 from the membrane into the nucleus. Nitric oxide attaches to the CLIC4 protein by a process called S-nitrosation thereby modifying the protein’s structure.
“Broadly speaking, we aim to synthesise, purify and characterise the human CLIC4 protein using methods previously attempted by Littler and co-workers. Thereafter, we would need to identify the sites where S-nitrosation is likely to occur on the CLIC4 protein.”
Mathura’s strategy is to modify the site on the CLIC4 protein where S-nitrosation occurs, using site-directed mutagenesis and then compare this protein to an unmodified CLIC4 in terms of structure and function.
“If we find out exactly how it works, how it moves in and out, then we can begin to understand its role in cancer and some neuro-degenerative diseases,” says Mathura.
Mathura completed her BSc Honours and MSc (cum laude) degrees at the University of Natal before moving to Wits in 2005. Here she completed her PhD in Bioinorganic Chemistry, working on vitamin B12 and related compounds. Two papers have been published from her PhD work. She is currently hosted at the PSFRU by Professor Heini Dirr.
How to survive extinction: Live fast, die young
- Wits University
Media release: National Museum examines life history of ancient mammal relatives.
Two hundred and fifty-two million years ago, a series of Siberian volcanoes erupted and sent the Earth into the greatest mass extinction of all time. Billions of tons of carbon were propelled into the atmosphere, radically altering the Earth’s climate.
Yet, some animals thrived in the aftermath and scientists now know why.
When combined with results from survivorship models, this observation leads the team to suggest that these animals bred at younger ages than their predecessors.
“Before the Permo-Triassic extinction, the therapsid Lystrosaurus had a life span of about 15 years based on the record of growth preserved in their bones,” said National Museum palaeontologist Jennifer Botha-Brink, the lead author on the paper. “Yet, nearly all of the Lystrosaurus specimens we find from after the extinction are only 2–3 years old. This implies that they must have been breeding when they were juveniles themselves.”
This adjustment in life history also meant a physical change for Lystrosaurus. Before the mass extinction, this creature would have been a couple of metres long and weighed hundreds of kilograms—about the size of a pygmy hippo. Post-extinction, its size dropped to that of a large dog, in large part due to its altered lifespan. Yet, these adaptations seemed to pay off for Lystrosaurus. Ecological simulations show that by breeding younger, Lystrosaurus could have increased its chance of survival by 40% in the unpredictable environment that existed in the aftermath of the extinction.
This change in breeding behavior is not isolated to ancient animals either. In the past century, the Atlantic cod has undergone a similar effect due to human interference. Industrial fishing has removed most large individuals from the population, shifting the average size of cod significantly downward. Likewise, the remaining individuals are forced to breed as early in their lives as possible. Similar shifts have also been demonstrated in African monitor lizards.
“With the world currently facing its sixth mass extinction, palaeontological research can help us understand how and why some animals, such as those like Lystrosaurus, thrived in the face of disaster,” said Botha-Brink. Studying the reasons for differential survival in response to dramatic environmental perturbation amongst extinct species will allow us to better predict how today’s climate change will affect modern species.”
Summary of Major Findings
Study of bone microstructure and body size distributions in the forerunners of mammals (therapsids) reveals distinct life history changes during the Permo-Triassic Mass Extinction (252 Mya).
Our results show that post-extinction species took less time to reach adult size, had shortened life expectancies, high mortality rates, and were at heightened risk of extinction.
Simulations using ecological modelling show that breeding earlier, which would have led to shortened generation times, could have helped therapsids survive in the unpredictable, resource-limited post-extinction environment, and explains body size distributions observed in earliest Triassic species like Lystrosaurus.
The results help explain how the “disaster taxon” Lystrosaurus, not only survived, but spread to all areas of the globe and became the most abundant vertebrate after the Permo-Triassic Mass Extinction.
Background Facts
There have been five major mass extinctions in Earth’s history.
The Permo-Triassic Mass Extinction (252 Mya) was the most catastrophic extinction in Phanerozoic history.
It killed 80-96% of all marine species and 70% of all terrestrial species.
Post-extinction ecosystems did not fully recover until some 5 million years after the event.
Therapsids include animals like Lystrosaurus, and another group called the cynodonts, which includes mammals and their immediate ancestors. Their body sizes ranged from that of a tiny mouse to a massive rhino. South Africa contains the best fossil record of early therapsids in the world.
The paper does NOT say
We do not demonstrate behavioural or physical evidence of early reproduction. Rather, our main empirical dataset comes from body size distributions and bone microstructure, which show direct evidence of shorter life expectancies in Triassic therapsids. Our inference of earlier breeding is then based on size distributions and expectations of survivorship models that we pursued based on our observations of the bone microstructure.
About the DST/NRF Centre of Excellence in Palaeosciences at Wits University
The DST/NRF Centre of Excellence (CoE) for the Palaeosciences was awarded in 2013 to the University of the Witwatersrand and its collaborating institutions, namely the University of Cape Town, Iziko Museum in Cape Town, the National Museum in Bloemfontein, the Albany Museum of Rhodes University, and Ditsong Museum in Pretoria. It is hosted in the Evolutionary Studies Institute at Wits University.
Over 170 posters and oral presentations vied for prizes at the 7th Postgraduate Cross-Faculty Symposium
Students who are on a quest for deeper knowledge and in pursuit of innovative solutions exhibited their research at the 7th Postgraduate Cross-Faculty Symposium, held in March where over 170 posters and oral presentations vied for prizes.
The Symposium was opened by Professor Mary Scholes, Director of Postgraduate Affairs who introduced the keynote speaker, Nonhlanhla Masina.
She is currently doing her masters in pharmaceutical sciences focusing on chemical modification methods for biopolymers for innovative application in drug delivery.
Prizes were awarded for the top three posters and orals in each Faculty. The top ten winners then competed in the cross-faculty presentations.
The first prize for the cross-Faculty oral presentations was shared between Ofentse Makgae from the Faculty of Health Sciences and Taahira Mangera from the Faculty of Engineering and the Built Environment.
Makgae holds numerous other awards under his name and is also the recipient of the 2016 Rhodes Scholarship where he will read for a Doctor of Philosophy degree in Materials Science at Oxford University.
This year, the judges were hard pressed at the Symposium to select the winners as they agreed that the quality of research presented has never been so high.
“The quality of the presentations was the highest it has ever been and all the students who participated should be praised and thanked for the effort they made to prepare world class posters and oral presentations,” says Scholes.
Professor Zeblon Vilakazi, the Deputy Vice-Chancellor Research and Postgraduate Affairs closed the Symposium with a prize giving and cocktail lunch.
Wits researchers celebrated
- Kemantha Govender
Wits University honoured a number of academics for their excellence in research and postgraduate supervision at a ceremony on Wednesday, 13 April 2016.
Professor Andrew Crouch, Deputy Vice-Chancellor: Academic, thanked the awardees for their immense contributions at the event that was held at the Parktown Education Campus. “It is through your achievements that we are seen in such high regard both nationally and internationally,” said Crouch.
Crouch's sentiments were echoed by his colleague Professor Zeblon Vilakazi, Deputy Vice-Chancellor: Research and Post Graduate Affairs, who said the Global South and the rest of Africa looks at Wits with an incredible measure of inspiration. Despite Wits doubling its number of NRF-rated researchers in recent years and the University’s continuous ascent in world rankings, Vilakazi believes the best is yet to come.
Professor Linda Richter, Director of the DST-NRF Centre of Excellence in Human Development and the keynote speaker, emphasised the significance of inter-disciplinary collaborations.
She said if global challenges are to be addressed, there needs to be more collaborative work with each party bringing the best their discipline can offer to the table.
“The division between the physical and social sciences is rapidly breaking down, as of those of qualitative and quantitative methods, and basic and applied research but without the loss of discipline specialisation,” said Richter.
She gave an example where a research paper that is currently being reviewed has been jointly authoured by a macroeconomist, a climatologist, a geographer and geneticist, noting that this situation was very different from when she first started working in public health.
Here is the list of researchers and academics that were honoured:
2016 A-RATED:
Professor AJ Mbembe
Professor F Luca
Professor L Manderson
Professor R Smith
Professor L Morris
2016 A-RE RATED:
Professor C Penn
Professor C Feldman
Professor JD Lewis-Williams
Professor RN Owen-Smith
2016 RATED:
Dr U Akpojivi
Professor S Allais
Dr PW Barmby
Dr KG Behrens
Professor M Benhura
Professor R Bolhar
Professor KD Breckenridge
Professor RL Brooksbank
Professor C Chipeta
Dr KP Creamer
Dr K Dixon
Dr LC Du Toit
Dr A Ely
Dr KG Harding
Professor RS Hetem
Dr S Hirano
Professor ABR Janse van Rensburg
Dr D Kar
Professor JA Kinnaird
Dr N Komin
Dr M Langa
Dr A Le Roux-Kemp
Dr CJ Letcher
Dr DA Ligaga
Professor CP Long
Dr P Magejo
Professor FM Maringe
Professor WJM Maroun
Professor CGP Mathew
Professor MO Mhango
Professor I Mhlambi
Professor K Milner
Dr SGK Moeno
Professor M Musemwa
Dr E Musenge
Professor H Myezwa
Professor D Ojwang
Dr BS Pyper
Professor F Raal
Dr CM Sheridan
Dr L Traill
Dr DJ Woodford
2016 RE-RATED:
Professor S Abelman
Dr R Ballard
Professor Y Ballim
Professor DE Ballot
Professor M Bamford
Dr DS Brooke
Professor M Byrne
Professor L Chimuka
Professor JF Cohen
Dr ASC Cornell
Professor S Currie
Professor PN Delius
Professor KD Erlwanger
Dr M Fernandes
Professor A Fuller
Professor RL Gibson
Professor S Hazelhurst
Professor AC Horn
Professor V Houliston
Professor A Ihunwo
Professor H Janks
Professor B Kana
Professor G Lee
Professor D Levendis
Professor EN Libhaber
Professor HM Marques
Dr L Micklesfield
Professor E Momoniat
Professor OQ Munro
Professor J Naicker
Dr M Naidoo
Dr GE Olwage
Professor M Papathanasopoulos
Professor N Pillay
Professor JL Potterton
Professor MS Rollnick
Professor K Sartorius
Professor Y Sayed
Professor K Sliwa-Hahnle
Professor CJ Thurman
Professor AE Todes
Professor B Urban
Professor JS Wafer
Professor ETW Witkowski
Professor AJ Woodiwiss
TOP MOST CITED RESEARCHER IN EACH FACULTY
Professor K Sartorius (CLM)
Professor J Muthu (EBE)
Professor F. J. Raal (HSc)
Professor G Finchilescu (Hum)
Professor J Vearey (Hum)
Professor B Mellado (Sc)
Professor S Abelman (Sc)
TOP POST GRADUATE SUPERVISOR IN EACH FACULTY
Professor P Pillay (CLM)
Professor T Stacey (EBE)
Professor C Tiemessen (HSc)
Professor C Penn (HUM)
Professor C De Koning (Sc)
Adam Habib elected to the American Academy of Arts and Sciences
- Wits University
Habib and Constitutional Court Justice Edwin Cameron are the only two South Africans of the 213 new members elected to the Academy.
Wits Vice-Chancellor and Principal, Adam Habib and Constitutional Court Judge Edwin Cameron are the only two South Africans who were elected among the 37 Foreign Honorary Members from 17 countries, who were selected into the American Academy of Arts and Sciences (AAAS).
Founded in 1780, the American Academy of Arts and Sciences is one of the America’s oldest learned societies and independent policy research centres, convening leaders from the academic, business, and government sectors to respond to the challenges facing the nation and the world.
Current Academy research focuses on higher education, the humanities, and the arts; science and technology policy; global security and energy; and American institutions and the public good. The Academy’s work is advanced by its elected members, who are leaders in the academic disciplines, the arts, business, and public affairs from around the world.
The 236th (2016) class of members also includes novelist Colm Tóibín, La Opinión Publisher and CEO Monica Lozano, jazz saxophonist Wayne Shorter, former Botswanan President Festus Mogae, and autism author and spokesperson Temple Grandin.
Other members of the 2016 class include winners of the Pulitzer Prize and the Wolf Prize; MacArthur and Guggenheim Fellowships; the Fields Medal; and the Grammy Award and National Book Award.
“It is an honour to welcome this new class of exceptional women and men as part of our distinguished membership,” said Don Randel, Chair of the Academy’s Board of Directors. “Their election affords us an invaluable opportunity to bring their expertise and knowledge to bear on some of the most significant challenges of our day. We look forward to engaging these new members in the work of the Academy.”
“In a tradition reaching back to the earliest days of our nation, the honour of election to the American Academy is also a call to service,” said Academy President Jonathan F. Fanton. “Through our projects, publications, and events, the Academy provides members with opportunities to make common cause with one another. We invite these newly elected members to participate in this important and rewarding work—and to help produce the useful knowledge for which the Academy’s 1780 charter calls.”
Get the full list of new members of the AAAS here.
Research training to improve public and population health receives a funding boost
- Wits University
Wellcome Trust grants aimed at stemming the ‘brain drain’ of the best African scientists.
Professor Sharon Fonn of the Wits School of Public Health, together with Professor Alex Ezeh, Executive Director for African Population and Health Research Center in Kenya, has received over R100 million to produce postgraduates and support universities to lead world-class multidisciplinary research in public health.
The R108,15 million (£5.25million) was awarded by the Wellcome Trust, through the DELTAS Africa initiative, to the Consortium for Advanced Research Training in Africa+ (CARTA). The grant is a continuation grant. It is the second grant that CARTA has received from the Wellcome Trust, but the first through the DELTAS Africa initiative.
The Wellcome Trust has committed R432 million (£21 million) to the DELTAS Africa initiative, which aims to improve health in Africa through research driven by the most urgent regional challenges. The funds were allocated to research teams in the Ivory Coast, Kenya, Senegal and Uganda to conduct world-class health research and train the future generation of the continent’s scientists.
CARTA, one of four recent research programmes in Africa that have been awarded grants, enroled it first students in 2010 and seeks to train and produce PhD graduates to lead world-class multidisciplinary research that makes a positive impact on public and population health.
“This additional grant allows us to consolidate and extend the gains that we have already made in CARTA,” said Fonn.
The consortium comprises nine African universities and four African Research Centres and selected northern partners enroled their first cohort of PhD fellows in 2010.
To date, CARTA has a total 140 PhD fellows, 24 of whom have graduated. Most of these graduates are either enroled in post-doctoral fellowships or have received re-entry grants to allow them to do research when they return to their jobs at universities. Nineteen Wits staff members have won CARTA fellowships and many more of the CARTA fellows are enroled as PhD students at Wits across five faculties.
“We have also worked with over 300 faculty members (librarians, registrars, finance and ICT staff) to promote a research supportive environment at member universities and have held six workshops with 121 supervisors to reinvigorate PhD supervision.”
Dr Jeremy Farrar, Director of the Wellcome Trust said: “Strengthening health research across sub-Saharan Africa is a powerful way to improve people’s lives in the continent and around the world. Health crises such as Ebola and now Zika, and long-standing threats such as malaria, TB, HIV and increasingly the non-communicable diseases, will only be solved with a strong research base to inform public health measures and develop new treatments and vaccines.”
By supporting the training of scientists within the continent, DELTAS Africa is seeking to stem the ‘brain drain’ of the best African scientists and promote the Africa-led development of world-class research leaders to solve the continent’s most pressing health needs.
Currently, Africa accounts for 15% of the global population and 25% of the global disease burden, but only produces about 2% of the world’s research output. A shortage of skilled personnel - Africa only has 79 scientists and engineers per million inhabitants, compared with 168 for Brazil, 2,457 for Europe and 4,103 for the United States- and limited infrastructure have contributed to the low research outputs.
DELTAS Africa will be handed over to Alliance for Accelerating Excellence Science in Africa in the second half of the year as part of its vision to shift the centre of gravity and decision-making process to the continent.
