Tag Archives: public health

Spanner in the works for a parasite motor

Throughout World Antimicrobial Awareness Week, we’re featuring key areas of research at Birkbeck relating to the management of diseases. In this blog, we feature the work of former PhD student, Alex Cook, who is looking at new approaches to malaria control.

Alex Cook

Alex Cook

Separated by 85 million years of evolution, the parasite Plasmodium falciparum that causes the most deadly form of malaria, is a very different beast to its human host. Yet the challenge for malaria treatments is that they must kill the parasite but not destroy the cells of their human host in which the parasite hides. Malaria is a massive disease burden world-wide. Hundreds of thousands of people are killed each year, the majority of which are children younger than five. In Africa, disruption arising from the COVID-19 pandemic to existing measures also threatens to undo the last decade of malaria control. With resistance to current frontline therapeutics rapidly rising, new drug targets and vaccines are urgently needed.

Malaria-causing parasites are single cells and have a complex life-cycle within both human and mosquito hosts. The many iterations of parasite proliferation that are essential for disease transmission are driven by intracellular machinery called the mitotic spindle, which is built of cytoskeleton components called microtubules. This machinery ensures the correct distribution of replicated chromosomes to the newly produced cells. Targeting of the mitotic spindle by drugs is well-established in a variety of settings – notably human cancers – and components of the malaria proliferative machinery are thus attractive anti-parasite targets.

As part of his PhD work in the research group of Professor Carolyn Moores (Biological Sciences), Alex Cook studied a component of the malaria mitotic spindle machinery, a molecular motor called kinesin-5. Kinesin-5’s are a family of proteins known for their ability to ‘push and pull’ microtubules to create ordered structures within the cell. Alex used a very powerful electron microscope to take images of kinesin-5 molecules – which are around a millionth of a millimetre in size – bound to individual microtubules. He then used computational analysis to combine these pictures and calculate their three-dimensional shape, thereby providing information about how the motors work in the parasite themselves.

the Kinesin protein that contributes to malaria

Using this information, Alex – who is co-supervised by Professor Maya Topf and also collaborates with Dr Anthony Roberts, both also in Biological Sciences – showed that although the malaria kinesin-5 motor shares some functional properties with human kinesin-5, there are several key differences that indicate it might be susceptible to specific drug targeting. Confirming this idea, Alex found that a drug-like molecule that blocks human kinesin-5 activity does not affect the parasite motor.

Alex Cook, who is now a postdoctoral researcher at the University of Oxford said: “To uncover new approaches to malaria control, we urgently need to look at new molecules from the parasite. Using high resolution electron microscopy, this first look at a parasite cell division motor will provide a springboard for discovery of small molecules that can disrupt malaria replication.”

Professor Moores commented: “Alex’s hard work, together with vital support from our department’s lab and computational teams, demonstrates the power of electron microscopy to explore medically important challenges.”

Alex’s work was recently published in The Journal of Biological Chemistry (https://doi.org/10.1016/j.jbc.2021.101063). Future directions for the project involve further investigation of specific motor inhibitors, and also of the function of kinesin-5 in the parasite itself, in collaboration with the research group of Professor Rita Tewari at the University of Nottingham.

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Storm Train

Throughout Breast Cancer Awareness Month (October), the Building Resilience in Breast Cancer Centre (BRiC) is sharing stories, told first-hand by women who’ve experienced the illness. Here, Sara Williamson, Writer and Chair of the Mid-Yorkshire Breast Cancer Support Group, shares her journey.

image of Sara Williamson quote

So, after a mastectomy: node clearance (as 14/17 lymph nodes were affected), then chemotherapy, sepsis delaying radiotherapy, more surgery due to infections, Herceptin being stopped and started due to heart failure twice, then the Zoladex harpooning, followed by reconstruction, reduction, lypo filling – that filled four years from 2015 – 2019. That was the treatment plan! Nothing went in a straight line! The train kept derailing and diverting. Nothing prepares you for the side effects. Having to relearn to walk again and use my arms was an upward challenge.

Cancer disrupts your career, friendships and day to day living. I remember people being scared of me, the sad looks, no close proxemics. I was a reminder of the possibility of death and subjects always changed so that they did not have the burden of carrying my illness.

So, grade 3, stage 3c with a 40% chance of living. Five years was the predicted life expectancy, if I completed all treatment. I fought to continue treatment as was bloody minded enough to prove that those stats would be wrong. You would think after completing four years of treatment that you would be relieved, but the truth is that psychologically and emotionally the clock starts ticking backwards and the mind plays tricks on you. There’s the whisper in your ear that means that you have one year left to live, and reaching the five-year mark is supposed to be good, right!? People don’t realise that although alive you feel half dead with the side effects.

Every blood test recalled, mammogram, urine test and medical review terrifies me, so much so that there are sleepless nights until a recurrence is ruled out. When the word ‘cancer’ hangs over a cancer survivors head, it can be emotionally paralysing, making decision-making a challenge. New unexplained aches and pains cause fear of recurrence, and anxiety can be triggered by sounds and smells in hospital waiting rooms. Knowing your own body helps distinguish and recognise changes, but to what extent are we vigilant? Checking daily is obsessive but like a form of necessary obsessive compulsive disorder (OCD).

There’s emotional grief with enforced menopause and the loss of fertility, even if you never planned to have children. Body image, scars and disfigurement mean that you can’t relate to old friends in the same way. It’s difficult losing part of your body especially one so visible, and one which defines you as a woman. There’s frustration at life interrupted. Trying on bras and t-shirts that never seem to fit. Life and the body is lopsided.

Words all seem to have new meanings: ‘Warrior, fighter, survivor’. There’s no emphasis on one’s quality of life, or acquired disabilities, or new health issues. For secondary metastatic breast cancer patients, the word survivor seems to optimise the gift of life inappropriately. Then there’s guilt and grief at hearing of friends that have not lived. You are back on that storm train again.

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COVID-19 in prisons – a major public health risk

Catherine Heard, Director of the World Prison Research Programme at the Institute for Crime and Justice Policy Research (ICPR) at Birkbeck, discusses the impact of COVID-19 on prison populations.

Prison

The coronavirus pandemic presents formidable challenges for prisons worldwide – challenges they will struggle to meet, with potentially grave consequences for the health of prisoners, prison staff, their families, and all of us.

This is a fast-moving situation: since the outbreak was declared a pandemic on 12 March, prisoners and prison staff have tested positive in several European countries, and prisoners have died in England and France. These cases will only be the tip of the iceberg globally. With prison health systems in so many parts of the world struggling to provide even basic healthcare, many sick prisoners and prison staff will not have been tested. Overcrowded and under-resourced prisons offer the perfect conditions for the rapid spread of any contagious disease, including COVID-19, within and beyond their confines.

Last year, we published a report examining the effects of failed penal policies through the lens of health. We showed that well over 60% of countries have overcrowded prison systems (based on information held on our World Prison Brief database). Our research included evidence from ten diverse jurisdictions across five continents. Prisoners spoke of extreme overcrowding (for example, 60 men sharing cells built for 20 in Brazil); inadequate medical treatment, with too few doctors to deal even with routine health issues let alone serious disease outbreaks; constant hunger; lack of fresh air and exercise; shared buckets instead of toilets; not enough fresh water or soap; having to eat while seated on the toilet due to lack of space in a shared cell.

These are the realities of prisons across the world. They provide important context for the World Health Organisation’s warning that global efforts to tackle the spread of the disease may fail without proper attention to infection control inside prisons.

How have prison systems around the world responded to the pandemic? Many prison authorities – including in England & Wales – have suspended visits to prisoners, and cancelled temporary release schemes. In Columbia, Brazil, India, Italy, Romania and Lebanon, prisoners have rioted at these measures and in protest at the life-threatening conditions in which they are being held. Prisoner deaths, escapes and widespread violence have been reported.

More recently, some governments have responded by releasing prisoners: in Turkey, legislation was passed to release 100,000 of the country’s roughly 286,000 prisoners; similar steps have been taken in Iran and are under consideration in the United States, Canada and Ireland. In England and Wales, the government has so far declined to do this, despite the severe challenges already facing our overcrowded prison estate.

Now, detailed guidance from WHO, running to 32 pages, should leave no government in doubt about the serious risks presented by the virus, and how to tackle them. It states: ‘The risk of rapidly increasing transmission of the disease within prisons or other places of detention is likely to have an amplifying effect on the epidemic, swiftly multiplying the number of people affected.’ It calls for ‘strong infection prevention and control measures, adequate testing, treatment and care’ and provides detail on what this means in practice.

The parlous state in which prisons find themselves throughout the world today will make it difficult for them to follow the guidance, as they lack the resources – human, material, and financial – with which to do so. Even before the pandemic they were struggling to provide basic sanitation and healthcare for those in their care, as our research has shown.

COVID-19 provides the clearest illustration yet that prison health is public health. It is more important than ever for our governments and prison administrations to abide by the principle, enshrined in international law, that prisoners have an equal right to health and healthcare. Realistically, the only way that most countries could afford to meet this obligation is by first reducing their use of incarceration. This means ruling out custody for less serious, non-violent offending; and reversing the recent growth in the length of prison sentences.

It also means cutting substantially the use of pre-trial detention.  In America, thousands of the country’s nearly half a million pre-trial detainees are in jail for no better reason than that they cannot afford bail – although senator Kamala Harris has called for this to end.

No one should be remanded in custody unless absolutely necessary. But, of the more than three million people in pre-trial detention across the world, a large proportion are there purely because they cannot afford bail, or their country’s courts are hopelessly backlogged (a situation that will only worsen as courts around the world are forced to stop hearing all but the most urgent matters because of the current health emergency). On 2 April, we will release the latest global data on pre-trial prisoner numbers. It will reveal a significant upward trend, and should provide a wake-up call for governments the world over.

All news items and other sources referred to in this piece can be accessed via a dedicated COVID-19 page on ICPR’s World Prison Brief database: https://www.prisonstudies.org/news/news-covid-19-and-prisons

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