In Memory of Dr Alan Nicholls (1947-2014)

Alan Nicholls

Alan Charles Nicholls

18th September 1947 – 16th May 2014


It was with great sadness that I heard last month of the passing of Dr Alan Nicholls at the relatively young age of 67. Alan was my PhD supervisor and mentor from 1989-1992 and I remember him and those times at the MRC-CRC with great fondness.

Regrettably I lost contact with Alan after his early retirement from science in 2001, but it is very true that you learn by example and I am reminded of him on an almost daily basis as I supervise the next generation of young scientists, who will hopefully occupy my office one day!

I don’t ever remember Alan showing disappointment or raising his voice, despite (numerous) mistakes that I made during these early steps in my scientific career. Alan was forever encouraging and always saw the positive in every failed experiment; how else can you learn?

Alan had a great sense of humour and would always tolerate my (almost incessant) rambling about (yorkshire) cricket; at one point calling out, in his best ‘yorkshire’ accent, “Aye lad, there ain’t a yorkshireman born that can play cricket!”.

Alan of course was a great family man and always put his two kids first. As a single parent it was not easy to juggle work and home responsibilities; having said that his work ethic and scientific output was still second to none!


Alan undertook his PhD with Professor Henry Rydon in the Department of Chemistry at the University of Exeter entitled “the interaction of glutaraldehyde with amino-acids and proteins”. He then moved with his wife Helen to the USA and undertook post-doctoral research at the NIH Institute of Dental Research in Bethesda between 1971-1974; alongside other future collagen experts such as Peter Byers and David Rowe. Returning to the UK Alan worked with Alan Bailey and Vic Duance at the Agricultural Research Council laboratories in Langford near Bristol from 1974 to 1978.

In 1978 Alan moved from the ARC centre at Langford to the MRC Clinical Research Centre in Harrow to work with Mike Pope on defining the biochemical basis of certain inherited defects of connective tissue, especially vascular Ehlers Danlos syndrome and osteogenesis imperfecta (OI). Alan and Mike had previously met at the NIH in 1973, when Alan (who worked with Karl Piez) and Mike, who was on secondment from Victor McKusick’s group at Johns Hopkins, had explored certain inherited connective tissue diseases with George Martin.

At Harrow, there quickly followed a series of three letters published in The Lancet between 1979 and 1980 describing their early ground breaking work on the biochemical analysis of OI. Indeed, the 1979 letter reported the novel finding of completely deficiency alpha-2 chains of type I collagen in severe OI. Later they showed that the proband’s heterozygous first cousin parents had early osteoporosis. In various follow up studies of patients Alan demonstrated that a range of different connective tissues diseases could result from abnormal processing of collagens including Ehlers Danlos and cerebral aneurisms. In 1984 a seminal article published in the British Medical Journal demonstrated that an abnormal collagen alpha-chain contained a cysteine residue and thus becoming the first description of a collagen structural mutation. By the mid 1980s the group, originally called the “MRC Dermatology Research Group”, had changed its name to the “MRC Connective Tissue Genetics Group” and were fast embracing the new recombinant DNA technologies. By the late 1980s and early 1990s the group were regularly identifying new mutations in the genes encoding types I, III and V collagen and translating this new knowledge into more accurate genetic counseling of UK patients referred for clinical categorization. At this time they also hosted the early clinical and laboratory activities of Dr Anne de Paepe, who spent a fruitful sabbatical in Harrow and who later seconded several of her laboratory staff to the MRC Harrow laboratory.

Following the closure of the MRC Clinical Research Centre in September 1994, Alan moved with various other members of the Connective Tissue Genetics Group to the Strangeways Research Laboratory, where the group was part of the Department of Pathology at the University of Cambridge. In 1997, when it became apparent that the MRC did not plan to fund further connective tissue research after 2001, Alan and some group members moved from Strangeways to the University Pathology Laboratories at Tennis Court Rd. Alan continued to characterise the genetic and biochemical basis of human connective tissues diseases until his premature retirement in 2001. His final preliminary finding, which unfortunately he did not get the opportunity to confirm before retirement, was the role of BMP1 mutations in recessive forms of OI; it would have been a well-deserved swan song. Other spin-offs of the group’s activities still continue in Cambridge where Allan Richards, who worked at Harrow and Cambridge, now oversees the molecular biology of Sticklers Syndrome.

The partnership between Alan and Mike forged new ground in our understanding of a variety of connective tissue disorders, particularly forms of EDS and OI.  For several years it was one of the strongest partnerships and one of the most productive in the world in defining the genetics and biochemistry of these disorders and some of these papers remain classics to this day.

Alan was always willing and happy to share his knowledge and expertise with colleagues and he trained numerous research scientists both from the UK and overseas. He forged strong links with other research groups, most notably in Belgium where he had also acted as an external examiner. Alan was an excellent supervisor and he mentored several successful PhD students whilst at Harrow, including Sara Daw and Mike Briggs.

Following his early retirement, Alan had time to concentrate on being a grandparent; his first granddaughter being only 2 years old at the time. When he wasn’t being an active granddad he spent lots of time on his bikes, a passion that developed out of the necessity to travel to Harrow for work each day. He would often be riding for hours at a time, or could be found performing maintenance in the garage. He was a great help when it came to homework for both his children and grandchildren; there didn’t seem to be much he didn’t know on any subject! He was also excellent at DIY due to his perfectionist nature, and he was often called upon by the family to help out with kitchen fitting and general home improvement projects. He had a passion for reading crime novels, and enjoyed the Scandinavian thrillers on TV. When Alan’s grandson came along, he got involved again and was often found supporting on the sidelines at junior football games. Alan often met up with old colleagues from his Cambridge days and more recently had joined a local quiz team.

Alan was a kind, funny, dependable, reliable, knowledgeable man, who kept his family at the heart of everything he did. Family, friends and colleagues alike will sorely miss him.

(Michael Briggs, Mike Pope, Frances and Paul Nicholls)


 

Clinical symptoms of MED patients caused by MATN3 and COMP gene mutations

Interesting paper from the group in Korea……BMC article

The medical records and radiographs of 59 molecularly confirmed multiple epiphyseal dysplasia (MED) patients were reviewed along with questionnaire surveys or telephone interviews.

Several very interesting and important correlations were identified:-

  • There appeared to be no difference in age of onset of symptoms; 8 years for both COMP and MATN3 mutations.
  • MED patients with COMP mutations were significantly shorter.
  • Hip pain and limitation of daily activity were more frequent in MED patients with COMP mutations.
  • Clinical symptoms of MED caused by MATN3 mutations were milder that the symptoms of COMP mutations.

And importantly………

“These differences in clinical manifestation and prognosis justify molecular differentiation between the two genotypes”.

The full article can be downloaded here 1471-2474-15-84

A new model system for limb development?

Here @ skeletal genetics we have decided to invest in a new model system to study limb development.

There are some distinct advantages such as a short gestation period and large numbers of offspring – ideal for genetic screens.

And we can enjoy the by product for breakfast.

However, there is a sting in the tail………….no pun intended…….

Such as a lack of suitable reagents……………but we will rely on the non-specificty of Santa Cruz antibodies to overcome this minor weakness.

bees